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Polyglutamine (polyQ)-mediated spinocerebellar ataxia (SCA), including SCA1, 2, 3, 6, 7, and 17, are caused by mutant genes with expanded CAG repeats, leading to the intracellular accumulation of aggregated proteins, the production of reactive oxygen species, and cell death. Among SCA, SCA3 is caused by a mutation in the ATXN3 (ataxin-3) gene. In a circumstance of polyQ aggregation, the autophagic pathway is induced to degrade the aggregated proteins, thereby suppressing downstream deleterious effects and promoting neuronal survival. In this study, we tested the effects of synthetic indole (NC009-1, -2, -3, -6) and coumarin (LM-022, -031) derivatives as chemical chaperones to assist mutant ATXN3-Q75 folding, as well as autophagy inducers to clear aggregated protein. Among the tested compounds, NC009-1, -2, and -6 and LM-031 interfered with Escherichia coli-derived ATXN3-Q75 aggregation in thioflavin T binding and filter trap assays. In SH-SY5Y cells expressing GFP-fused ATXN3-Q75, these compounds displayed aggregation-inhibitory and neurite growth-promoting potentials compared to untreated cells. Furthermore, these compounds activated autophagy by increasing the phosphatidylethanolamine-conjugated LC3 (microtubule associated protein 1 light chain 3)-II:cytosolic LC3-I ratio in these cells. A biochemical co-immunoprecipitation assay by using a mixture of HEK 293T cell lysates containing recombinant ATXN3-Q75-Venus-C-terminus (VC) or Venus-N-terminus (VN)-LC3 protein indicated that NC009-1 and -2 and LM-031 served as an autophagosome-tethering compound (ATTEC) to interact with ATXN3-Q75 and LC3, and the interaction was further confirmed by bimolecular fluorescence complementation analysis in cells co-expressing both ATXN3-Q75-VC and VN-LC3 proteins. The study results suggest the potential of NC009-1 and -2 and LM-031 as an ATTEC in treating SCA3 and, probably, other polyQ diseases. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is characterized by progressive involuntary chorea movements and cognitive decline. Recent research indicates that metabolic disturbance may play a role in its pathogenesis. Bile acids, produced during cholesterol metabolism in the liver, have been linked to neurodegenerative conditions. This study investigated variations in plasma bile acid profiles among individuals with HD. Plasma levels of 16 primary and secondary bile acids and their conjugates were analyzed in 20 healthy controls and 33 HD patients, including 24 with symptoms (symHD) and 9 carriers in the presymptomatic stage (preHD). HD patients exhibited significantly higher levels of glycochenodeoxycholic acid (GCDCA) and glycoursodeoxycholic acid (GUDCA) compared to healthy controls. Conversely, isolithocholic acid levels were notably lower in the HD group. Neurotoxic bile acids (glycocholic acid (GCA) + glycodeoxycholic acid (GDCA) + GCDCA) were elevated in symHD patients, while levels of neuroprotective bile acids (ursodeoxycholic acid (UDCA) + GUDCA + tauroursodeoxycholic acid (TUDCA)) were higher in preHD carriers, indicating a compensatory response to early neuronal damage. These results underscore the importance of changes in plasma bile acid profiles in HD and their potential involvement in disease mechanisms. The identified bile acids (GCDCA, GUDCA, and isolithocholic acid) could potentially serve as markers to distinguish between HD stages and healthy individuals. Nonetheless, further research is warranted to fully understand the clinical implications of these findings and their potential as diagnostic or therapeutic tools for HD. [ABSTRACT FROM AUTHOR]

Background: Approximately 10% to 20% of myasthenia gravis (MG) patients have experienced a myasthenic crisis (MC), which contributes to morbidity and mortality. MC triggered by infection is associated with poor outcomes. However, there is a lack of prognostic factors that clinicians can utilize to target interventions for preventing recurrent infection-triggered MC. This study aimed to characterize clinical manifestations, comorbidities, and biochemical profiles associated with recurrent infection-triggered MC in MG patients. Methods: This retrospective study included 272 MG patients hospitalized with an infection requiring at least 3 days of antibiotics from January 2001 to December 2019. Patients were further stratified into non-recurrent or recurrent infection groups. Clinical features such as gender, age, concomitant diseases, acetylcholine receptor antibodies and biochemical data (including electrolytes and coagulants), muscle strength of pelvic and shoulder girdle, bulbar and respiratory function, management with an endotracheal tube, Foley catheter, or plasmapheresis, duration of hospitalization, and culture pathogens were recorded. Results: The recurrent infection group was significantly older than the non-recurrent group (median age, 58.5 versus 52.0 years). Pneumonia was the most common infection and Klebsiella pneumoniae was the most common pathogen. The presence of concomitant diabetes mellitus, activated partial thromboplastin time prolongation, the duration of hospitalization, and hypomagnesaemia were independently associated with recurrent infection. The presence of deep vein thrombosis, thymic cancer, and electrolyte imbalances i.e., hypokalemia, and hypoalbuminemia were significantly associated with a risk for infection. The influence of endotracheal intubation, anemia, and plasmapheresis during hospitalization were inconsistent. Conclusions: The independent risk factors for recurrent infections in MG patients identified in this study include the presence of concomitant diabetes mellitus, hypomagnesaemia, activated partial thromboplastin time prolongation, and longer duration of hospitalization, highlighting the need for targeted interventions to prevent recurrent infections in this population. Further research and prospective studies are warranted to validate these findings and refine interventions for optimizing patient care. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a progressive and devastating neurodegenerative disease marked by inheritable CAG nucleotide expansion. For offspring of HD patients carrying abnormal CAG expansion, biomarkers that predict disease onset are crucially important but still lacking. Alteration of brain ganglioside patterns has been observed in the pathology of patients carrying HD. Here, by using a novel and sensitive ganglioside-focused glycan array, we examined the potential of anti-glycan auto-antibodies for HD. In this study, we collected plasma from 97 participants including 42 control (NC), 16 pre-manifest HD (pre-HD), and 39 HD cases and measured the anti-glycan auto-antibodies by a novel ganglioside-focused glycan array. The association between plasma anti-glycan auto-antibodies and disease progression was analyzed using univariate and multivariate logistic regression. The disease-predictive capacity of anti-glycan auto-antibodies was further investigated by receiver operating characteristic (ROC) analysis. We found that anti-glycan auto-antibodies were generally higher in the pre-HD group when compared to the NC and HD groups. Specifically, anti-GD1b auto-antibody demonstrated the potential for distinguishing between pre-HD and control groups. Moreover, in combination with age and the number of CAG repeat, the level of anti-GD1b antibody showed excellent predictability with an area under the ROC curve (AUC) of 0.95 to discriminate between pre-HD carriers and HD patients. With glycan array technology, this study demonstrated abnormal auto-antibody responses that showed temporal changes from pre-HD to HD. [ABSTRACT FROM AUTHOR]

Background: The effects of combined training can be affected by training characteristics such as frequency, session length, and duration. No empirical studies to date have directly compared how combined physical and cognitive training offered at different training frequencies affects cognitive function for older adults with cognitive decline. This study investigated the impact of training frequency on cognitive outcomes after combined physical and cognitive training for older adults with cognitive decline. Methods: A quasi-experimental study was conducted in community facilities and day care centers. The study assigned 89 older adults with cognitive decline into high-frequency (HF) or low-frequency (LF) training groups. The participants received 90- to 105-min training sessions, one (LF) or three (HF) times a week, for 12 weeks. Outcome measures were the Montreal Cognitive Assessment, Word List subtest of the Wechsler Memory Scale, Digit Symbol Substitution Test (DSST), and Stroop Color Word Test. Results: The HF group demonstrated greater improvement in immediate memory measured by the WL-IM (F = 8.7, P = 0.004) and in executive function measured by the SCWT (F = 5.89, P = 0.017) than the LF group. Compared with the HF group, the LF group showed a great improvement in delayed memory measured by the WL-DM (F = 9.62, P = 0.003). The HF and LF groups both increased in processing speed and global cognitive function. Conclusions: Our study indicated that the different training frequency of combined physical and cognitive training may result in benefits on different cognitive functions in older adults with cognitive decline. These findings may assist clinical practitioners in choosing appropriate training frequencies based on various intervention purposes for the elderly with cognitive decline. Trial registration: ClinicalTrials.gov Identifier NCT03619577 (08/08/2018). [ABSTRACT FROM AUTHOR]

Alterations in lipid composition and disturbed lipoprotein metabolism are involved in the pathomechanism of Huntington's disease (HD). Here, we measured 112 lipoprotein subfractions and components in the plasma of 20 normal controls, 24 symptomatic (sympHD) and 9 presymptomatic (preHD) HD patients. Significant changes were found in 30 lipoprotein subfractions and components in all HD patients. Plasma levels of total cholesterol (CH), apolipoprotein (Apo)B, ApoB-particle number (PN), and components of low-density lipoprotein (LDL) were lower in preHD and sympHD patients. Components of LDL4, LDL5, LDL6 and high-density lipoprotein (HDL)4 demonstrated lower levels in preHD and sympHD patients compared with controls. Components in LDL3 displayed lower levels in sympHD compared with the controls, whereas components in very low-density lipoprotein (VLDL)5 were higher in sympHD patients compared to the controls. The levels of components in HDL4 and VLDL5 demonstrated correlation with the scores of motor assessment, independence scale or functional capacity of Unified Huntington's Disease Rating Scale. These findings indicate the potential of components of VLDL5, LDL3, LDL4, LDL5 and HDL4 to serve as the biomarkers for HD diagnosis and disease progression, and demonstrate substantial evidence of the involvement of lipids and apolipoproteins in HD pathogenesis. [ABSTRACT FROM AUTHOR]

Neuroinflammation and oxidative stress have been emerging as important pathways contributing to Parkinson's disease (PD) pathogenesis. In PD brains, the activated microglia release inflammatory factors such as interleukin (IL)-β, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide (NO), which increase oxidative stress and mediate neurodegeneration. Using 1-methyl-4-phenylpyridinium (MPP+)-activated human microglial HMC3 cells and the sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, we found the potential of indole derivative NC009-1 against neuroinflammation, oxidative stress, and neurodegeneration for PD. In vitro, NC009-1 alleviated MPP+-induced cytotoxicity, reduced NO, IL-1β, IL-6, and TNF-α production, and suppressed NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in MPP+-activated HMC3 cells. In vivo, NC009-1 ameliorated motor deficits and non-motor depression, increased dopamine and dopamine transporter levels in the striatum, and reduced oxidative stress as well as microglia and astrocyte reactivity in the ventral midbrain of MPTP-treated mice. These protective effects were achieved by down-regulating NLRP3, CASP1, iNOS, IL-1β, IL-6, and TNF-α, and up-regulating SOD2, NRF2, and NQO1. These results strengthen the involvement of neuroinflammation and oxidative stress in PD pathogenic mechanism, and indicate NC009-1 as a potential drug candidate for PD treatment. [ABSTRACT FROM AUTHOR]

Introduction/Aims: A model for predicting responsiveness to immunotherapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) has not been well established. We aimed to establish a new classifier for CIDP patients based on clinical characteristics, laboratory findings, and electrophysiological features. Methods: The clinical, laboratory, and electrophysiological features of 172 treatment‐naïve patients with CIDP between 2003 and 2019 were analyzed using an unsupervised hierarchical clustering. The identified pivotal features were used to establish simple classifications using a tree‐based model. Results: Three clusters were identified: 1, n = 65; 2, n = 70; and 3, n = 37. Patients in Cluster 1 scored lower on the disability assessment score before treatment. More patients in Clusters 2 (90.0%) fulfilled demyelinating criteria than patients in Cluster 1 (30.8%, p <.001). Cluster 3 had more patients with chronic kidney disease (CKD) (27.0%) and hypoalbuminemia (3.40 g/dL) than did Cluster 2 (CKD: 0%, p <.001; hypoalbuminemia: 4.09 g/dL, p <.001). The responsiveness to pulse steroid therapy was higher in Cluster 2 (70.0%) than in Clusters 1 (31.8%; p =.043) and 3 (25.0%; p =.014). A tree‐based model with four pivotal features classified patients in our cohort into new clusters with high accuracy (89.5%). Discussion: The established hierarchical clustering with the tree‐based model identified key features contributing to differences in disease severity and response to pulse steroid therapy. This classification system could assist clinicians in the selection of treatments and could also help researchers by clustering patients for clinical treatment trials. [ABSTRACT FROM AUTHOR]

Background: Postpartum spinal cord infarction is a very rare disease. Only two cases have been reported in the English literature. Methods: We reported a 26 year old female who received second doses of the mRNA-1273 vaccine 52 days before delivery. She presented as sudden onset of paraplegia, sensory level, and sphincter incontinence at postpartum period. No history of heparin exposure was noted. Imaging findings confirmed the T10-11 level infarction and her anti–human heparin platelet factor 4 (anti-PF4) antibody was positive. After 7 days of dexamethasone therapy, her paraplegia and urinary incontinence gradually improved. Results: The CT angiography (CTA) of the artery of Adamkiewicz (Aka) showed tandem narrowing, most conspicuous at the T10-11 level, which was presumably due to partial occlusion of the arteriolar lumen. The thoracolumbar spine magnetic resonance imaging with contrast medium showed owl's eyes sign at the T10 and T11 levels. We compared our case with two other case reports from the literature. Conclusions: Post-partum spinal cord infarction with positive anti-PF4 antibody and relatively thrombocytopenia are the characteristics of our case. [ABSTRACT FROM AUTHOR]

Background: Postpartum spinal cord infarction is a very rare disease. Only two cases have been reported in the English literature. Methods: We reported a 26 year old female who received second doses of the mRNA-1273 vaccine 52 days before delivery. She presented as sudden onset of paraplegia, sensory level, and sphincter incontinence at postpartum period. No history of heparin exposure was noted. Imaging findings confirmed the T10-11 level infarction and her anti–human heparin platelet factor 4 (anti-PF4) antibody was positive. After 7 days of dexamethasone therapy, her paraplegia and urinary incontinence gradually improved. Results: The CT angiography (CTA) of the artery of Adamkiewicz (Aka) showed tandem narrowing, most conspicuous at the T10-11 level, which was presumably due to partial occlusion of the arteriolar lumen. The thoracolumbar spine magnetic resonance imaging with contrast medium showed owl's eyes sign at the T10 and T11 levels. We compared our case with two other case reports from the literature. Conclusions: Post-partum spinal cord infarction with positive anti-PF4 antibody and relatively thrombocytopenia are the characteristics of our case. [ABSTRACT FROM AUTHOR]

Background: Early‐onset Parkinson's disease (EOPD)/young‐onset Parkinson's disease (YOPD) is defined as Parkinson's disease (PD) with an age at onset (AAO) after age 21 years but before the usual AAO for PD. Consensus is lacking, and the reported maximal age for EOPD/YOPD has varied from 40 to 60 years, leading to a lack of uniformity in published studies and difficulty in harmonization of data. EOPD and YOPD have both been used in the literature, somewhat interchangeably. Objective: To define the nomenclature and AAO cutoff for EOPD/YOPD. Methods: An extensive review of the literature and task force meetings were conducted. Conclusions were reached by consensus. Results: First, the literature has seen a shift from the use of YOPD toward EOPD. This seems motivated by an attempt to avoid age‐related stigmatization of patients. Second, in defining EOPD, 56% of the countries use 50 or 51 years as the cutoff age. Third, the majority of international genetic studies in PD use an age cutoff of younger than 50 years to define EOPD. Fourth, many studies suggest that changes in the estrogen level can affect the predisposition to develop PD, making the average age at menopause of 50 years an important factor to consider when defining EOPD. Fifth, considering the differential impact of the AAO of PD on professional and social life, using 50 years as the upper cutoff for the definition of EOPD seems reasonable. Conclusions: This task force recommends the use of EOPD rather than YOPD. It defines EOPD as PD with AAO after 21 years but before 50 years. [ABSTRACT FROM AUTHOR]

Background: Isaacs' syndrome is a peripheral nerve hyperexcitability (PNH) syndrome due to peripheral motor nerve instability. Acquired Isaacs' syndrome is recognized as a paraneoplastic autoimmune disease with possible pathogenic voltage-gated potassium channel (VGKC) complex antibodies. However, the longitudinal correlation between clinical symptoms, VGKC antibodies level, and drug response is still unclear. Case presentation: A 45-year-old man had progressive four limbs soreness, muscle twitching, cramps, and pain 4 months before admission. Electromyography (EMG) studies showed myokymic discharges, neuromyotonia, and an incremental response in the high-rate (50 Hz) repetitive nerve stimulation (RNS) test. Isaacs' syndrome was diagnosed based on clinical presentations and EMG reports. Serum studies showed positive VGKC complex antibodies, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. The acetylcholine receptor antibody was negative. Whole-body computed tomography (CT) and positron emission tomography revealed a mediastinal tumor with the great vessels encasement, right pleura, and diaphragm seeding. Biopsy confirmed a World Health Organization type B2 thymoma, with Masaoka stage IVa. His symptoms gradually improved and both LGI1 and CASPR2 antibodies titer became undetectable after concurrent chemoradiotherapy (CCRT) and high dose steroid treatment. However, his Isaacs' syndrome recurred after the steroid was reduced 5 months later. Follow-up chest CT showed probable thymoma progression. LGI1 antibody turned positive again while CASPR2 antibody remained undetectable. Conclusions: Our patient demonstrates that Isaacs' syndrome could be the initial and only neuromuscular manifestation of malignant thymoma. His Isaacs' syndrome is correlated well with the LGI1 antibody level. With an unresectable thymoma, long-term immunosuppressant therapy may be necessary for the management of Isaacs' syndrome in addition to CCRT for thymoma. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD), a degenerative disease with irreversible motor dysfunction, impacts patients' quality of life (QoL). Spirituality can provide a sense of hope and meaning when individuals are faced with adverse life events, such as a diagnosis of PD. However, few studies have examined the relationship between spiritual well-being and QoL for persons with PD. Objective: To explore the relationships between the disease characteristics, spirituality and QoL for persons with PD, and verify the mediating effects of spirituality on the relationship. Methods: This cross-sectional study recruited patients with PD (n = 110) by convenience sampling from a neurological clinic in northern Taiwan. Variables were measured using the Spirituality Index of Well-Being Chinese version (SIWB-C) and the 39-item Parkinson's disease Quality of Life Questionnaire Chinese version (PDQ-39-C) self-report questionnaires. Descriptive analysis and linear hierarchical regression were conducted to examine the studied variables and explore the mediating effect of spiritual wellbeing. Results: Those whose scores were significantly better in PDQ-39 were younger, employed, with shorter disease duration and less severe condition with better functioning on their early stages and lower LEDD; additionally, those who had better quality of life also experienced better spiritual wellbeing than the counterparts. The regression model demonstrated spiritual self-efficacy had mediating effects between disease characteristics and QoL, explaining 69.8%of the variance (adjusted R2 = 65.3%). Conclusion: The results can be the references for future strategies and interventions, focusing on increasing spiritual self-efficacy and reducing the impact of disease severity to improve QoL for persons with PD. [ABSTRACT FROM AUTHOR]

Background: Neuromuscular ultrasound is a complementary technology that aids in the diagnosis of peripheral neuropathy. The interpretation of neuromuscular ultrasound results requires the use of accurate normative cross-sectional area (CSA) reference values. This study aims to provide CSA reference values specific to Taiwanese adults for Sonography of peripheral nerves in the upper and lower extremities. Methods: The study cohort included 66 healthy subjects (36 women; 30 men). A linear probe was used to measure the CSA of the median, ulnar, radial, tibial, sural, and peroneal nerves at multiple sites. These data were analyzed to determine standard ranges for the CSA at each site (reference range = mean ± 2 × SD) and identify correlations between the CSA and patient characteristics. Results: Normative CSA ranges were determined for all the assessed nerve sites, revealing that the nerve sizes in this Taiwanese population were smaller than Caucasian populations but comparable to those reported for other Asian cohorts. Men tended to have larger nerves than women, even after adjusting for height and weight. The size of ulnar nerve in the cubital tunnel and the peroneal nerve in the popliteal fossa correlated negatively with increasing age. The nerve size correlated positively with increasing weight and BMI at several sites, correlation of median nerve in the forearm with weight and BMI was significant after multiple testing. Significant correlation was also found between size of ulnar nerve in cubital tunnel and decreasing height. Conclusion: We provide reference ranges for neuromuscular ultrasound CSA values for the upper and lower extremities that are specific to the Taiwanese population. These reference values may be useful for evaluating peripheral neuropathy in Taiwanese subjects. [ABSTRACT FROM AUTHOR]

Microstructure damage in white matter might be linked to regional and global atrophy in Huntington's Disease (HD). We hypothesize that degeneration of subcortical regions, including the basal ganglia, is associated with damage of white matter tracts linking these affected regions. We aim to use fixel-based analysis to identify microstructural changes in the white matter tracts. To further assess the associated gray matter damage, diffusion tensor-derived indices were measured from regions of interest located in the basal ganglia. Diffusion weighted images were acquired from 12 patients with HD and 12 healthy unrelated controls using a 3 Tesla scanner. Reductions in fixel-derived metrics occurs in major white matter tracts, noticeably in corpus callosum, internal capsule, and the corticospinal tract, which were closely co-localized with the regions of increased diffusivity in basal ganglia. These changes in diffusion can be attributed to potential axonal degeneration. Fixel-based analysis is effective in studying white matter tractography and fiber changes in HD. [ABSTRACT FROM AUTHOR]

Background: Patients with Parkinson's disease (PD) can develop impulse control disorders (ICDs) while undergoing a pharmacological treatment for motor control dysfunctions with a dopamine agonist (DA). Conventional clinical interviews or questionnaires can be biased and may not accurately diagnose at the early stage. A wearable electroencephalogram (EEG)-sensing headset paired with an examination procedure can be a potential user-friendly method to explore ICD-related signatures that can detect its early signs and progression by reflecting brain activity.Methods: A stereotypical Go/NoGo test that targets impulse inhibition was performed on 59 individuals, including healthy controls, patients with PD, and patients with PD diagnosed by ICDs. We conducted two Go/NoGo sessions before and after the DA-pharmacological treatment for the PD and ICD groups. A low-cost LEGO-like EEG headset was used to record concurrent EEG signals. Then, we used the event-related potential (ERP) analytical framework to explore ICD-related EEG abnormalities after DA treatment.Results: After the DA treatment, only the ICD-diagnosed PD patients made more behavioral errors and tended to exhibit the deterioration for the NoGo N2 and P3 peak amplitudes at fronto-central electrodes in contrast to the HC and PD groups. Particularly, the extent of the diminished NoGo-N2 amplitude was prone to be modulated by the ICD scores at Fz with marginal statistical significance (r = - 0.34, p = 0.07).Conclusions: The low-cost LEGO-like EEG headset successfully captured ERP waveforms and objectively assessed ICD in patients with PD undergoing DA treatment. This objective neuro-evidence could provide complementary information to conventional clinical scales used to diagnose ICD adverse effects. [ABSTRACT FROM AUTHOR]

Our study aimed to investigate the incidence, risk factors and time to occurrence of malignancy in patients with dermatomyositis (DM) and polymyositis (PM). The electronic medical records of 1100 patients with DM and 1164 patients with PM were studied between January 2001 and May 2019. Malignancies after myositis were diagnosed in 61 (5.55%) patients with DM and 38 (3.26%) patients with PM. The cumulative incidence of malignancies in patients with DM were significantly higher than patients with PM (hazard ratio = 1.78, log-rank p = 0.004). Patients with DM had a greater risk of developing malignancy than those with PM at 40–59 years old (p = 0.01). Most malignancies occurred within 1 year after the initial diagnosis of DM (n = 35; 57.38%). Nasopharyngeal cancer (NPC) was the most common type of malignancy in patients with DM (22.95%), followed by lung, and breast cancers. In patients with PM, colorectal, lung and hepatic malignancies were the top three types of malignancy. The risk factors for malignancy included old age (≥ 45 years old) and low serum levels of creatine phosphokinase (CPK) for patients with DM and male sex and low serum levels of CPK for patients with PM. Low serum levels of CPK in patients with myositis with malignancy represented a low degree of muscle destruction/inflammation, which might be attributed to activation of the PD-L1 pathway by tumor cells, thus inducing T-cell dysfunction mediating immune responses in myofibers. A treatment and follow-up algorithm should explore the occurrence of malignancy in different tissues and organs and suggested annual follow-ups for at least 5.5 years to cover the 80% cumulative incidence of malignancy in patients with DM and PM. [ABSTRACT FROM AUTHOR]

Objectives: Blood–brain barrier (BBB) disruption is a critical pathological process involved in neuromyelitis optica spectrum disorder (NMOSD). Here, we characterized the profile of five cell adhesion molecules in patients with NMOSD. Methods: We measured levels of cell adhesion molecules, including ICAM‐1, ICAM‐2, VCAM‐1, PECAM‐1, and NCAM‐1, in the serum of 28 patients with NMOSD, 24 patients with multiple sclerosis (MS), and 25 healthy controls (HCs). Results: ICAM‐2 levels (median: 394.8 ng/mL) were increased in patients with NMOSD compared with MS (267.1 ng/mL, P = 0.005) and HCs (257.4 ng/mL, P = 0.007), and VCAM‐1 and ICAM‐1 levels were higher in patients with NMOSD (641.9 ng/mL and 212.7 ng/mL, respectively) compared with HCs (465 ng/mL [P = 0.013] and 141.8 ng/mL [P = 0.002], respectively). However, serum PECAM‐1 levels were lower in patients with NMOSD (89.62 ng/mL) compared with MS (106.9 ng/mL, P = 0.015) and HCs (107.2 ng/mL, P = 0.007). Receiver operating characteristic curve analysis revealed that PECAM‐1 (area under the curve (AUC): 0.729) and ICAM‐2 (AUC: 0.747) had adequate abilities to distinguish NMOSD from MS, and VCAM‐1 (AUC: 0.719), PECAM‐1 (area under the curve: 0.743), ICAM‐1 (AUC: 0.778), and ICAM‐2 (AUC: 0.749) exhibited potential to differentiate NMOSD and HCs. Serum levels of PECAM‐1 also demonstrated a negative correlation with Kurtzke Expanded Disability Status Scale scores in patients with NMOSD. Interpretation: Our results reveal possible BBB breakdown signals specifically observed in NMOSD and highlight the potential role of cell adhesion molecules as biomarkers of this disease. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the progressive loss of dopaminergic (DAergic) neurons in the ventral brain. A disaccharide trehalose has demonstrated the potential to mitigate the DAergic loss in disease models for PD. However, trehalose is rapidly hydrolyzed into glucose by trehalase in the intestine, limiting its potential for clinical practice. Here, we investigated the neuroprotective potential of two trehalase-indigestible analogs, lactulose and melibiose, in sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treatment with MPTP generated significant motor deficits, inhibited dopamine levels, and down-regulated dopamine transporter (DAT) in the striatum. Expression levels of genes involved in anti-oxidative stress pathways, including superoxide dismutase 2 (SOD2), nuclear factor erythroid 2-related factor 2 (NRF2), and NAD(P)H dehydrogenase (NQO1) were also down-regulated. Meanwhile, expression of the oxidative stress marker 4-hydroxynonenal (4-HNE) was up-regulated along with increased microglia and astrocyte reactivity in the ventral midbrain following MPTP treatment. MPTP also reduced the activity of autophagy, evaluated by the autophagosomal marker microtubule-associated protein 1 light chain 3 (LC3)-II. Lactulose and melibiose significantly rescued motor deficits, increased dopamine in the striatum, reduced microglia and astrocyte reactivity as well as decreased levels of 4-HNE. Furthermore, lactulose and melibiose up-regulated SOD2, NRF2, and NQO1 levels, as well as enhanced the LC3-II/LC3-I ratio in the ventral midbrain with MPTP treatment. Our findings indicate the potential of lactulose and melibiose to protect DAergic neurons in PD. [ABSTRACT FROM AUTHOR]

Microtubule‐associated protein Tau, abundant in the central nervous system (CNS), plays crucial roles in microtubule assembly and stabilization. Abnormal Tau phosphorylation and aggregation are a common pathogenic hallmark in Alzheimer's disease (AD). Hyperphosphorylation of Tau could change its conformation and result in self‐aggregation, increased oxidative stress, and neuronal death. In this study, we examined the potential of licochalcone A (a natural chalcone) and five synthetic derivatives (LM compounds) for inhibiting Tau misfolding, scavenging reactive oxygen species (ROS) and providing neuroprotection in human cells expressing proaggregant ΔK280 TauRD‐DsRed. All test compounds were soluble up to 100 μM in cell culture media and predicted to be orally bioavailable and CNS‐active. Among them, licochalcone A and LM‐031 markedly reduced Tau misfolding and associated ROS, promoted neurite outgrowth, and inhibited caspase 3 activity in ΔK280 TauRD‐DsRed 293 and SH‐SY5Y cells. Mechanistic studies showed that LM‐031 upregulates HSPB1 chaperone, NRF2/NQO1/GCLC pathway, and CREB‐dependent BDNF/AKT/ERK/BCL2 pathway in ΔK280 TauRD‐DsRed SH‐SY5Y cells. Decreased neurite outgrowth upon induction of ΔK280 TauRD‐DsRed was rescued by LM‐031, which was counteracted by knockdown of NRF2 or CREB. LM‐031 further rescued the downregulated NRF2 and pCREB, reduced Aβ and Tau levels in hippocampus and cortex, and ameliorated cognitive deficits in streptozocin‐induced hyperglycemic 3 × Tg‐AD mice. Our findings strongly indicate the potential of LM‐031 for modifying AD progression by targeting HSPB1 to reduce Tau misfolding and activating NRF2 and CREB pathways to suppress apoptosis and promote neuron survival, thereby offering a new drug development avenue for AD treatment. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder related to nigrostriatal dopaminergic neuron degeneration and iron accumulation. As a cellular oxygen sensor, prolyl hydroxylase domain containing protein 2 (PHD2, encoded by egl-9 family hypoxia inducible factor 1, EGLN1) modifies hypoxia-inducible factor alpha (HIF-α) protein for proteasomal destruction under normoxic condition. In addition, 2-oxoglutarate- (OG-) dependent dioxygenase activity of PHD2 is involved in the oxygen and iron regulation of iron-responsive element binding protein 2 (IRP2) stability. Previously increased expression of EGLN1 was found in the substantia nigra of the parkinsonian brain. We investigated the possible role of c.380 G > C (p.C127S) of EGLN1 gene in Taiwanese patients with PD. 479 patients and 435 healthy controls were recruited. Polymerase chain reaction and BsmAI restriction enzyme analysis were applied for analysis. An association between CC genotype and reduced PD risk in the recessive model (CC vs. GG + GC) was found. Our study provides a link between EGLN1 c.380 G > C SNP and the development of PD. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease, and α-synuclein plays a critical role in the pathogenesis of PD. Studies have revealed controversial results regarding the correlation between motor severity and α-synuclein levels in peripheral blood from patients with PD. Objective: We examined α-synuclein levels in plasma or serum in patients with PD and investigated the relationship between plasma or serum α-synuclein level and motor symptom severity. Methods: We recruited 88 participants (48 patients with PD and 40 healthy controls). Clinical information was collected, and venous blood was drawn from each participant to be processed to obtain plasma or serum. The plasma or serum α-synuclein level was detected using monoclonal antibodies with magnetic nanoparticles, and was measured through immunomagnetic reduction. Plasma or serum α-synuclein levels were quantitatively detected. Results: In patients with PD, the means of plasma and serum α-synuclein level were 3.60 ± 2.53 and 0.03 ± 0.04 pg/mL, respectively. The areas under the receiver operating characteristic curve of plasma and serum α-synuclein for distinguishing patients with PD from healthy controls were 0.992 and 0.917, respectively. The serum α-synuclein level also showed a significant correlation with patients in H-Y stages 1–3 (r = 0.40, p = 0.025), implying that the serum α-synuclein level may be a potential marker of motor symptom severity in patients with early PD. Conclusions: Our data suggest that the α-synuclein level in serum or plasma can differentiate between healthy controls and patients with PD. Serum α-synuclein levels moderately correlate with motor severity in patients with early PD. [ABSTRACT FROM AUTHOR]

Non-motor symptoms of Parkinson's disease (PD) have been receiving increasing attention. Approximately half of patients with PD have experience PD-related pain. We investigated the effect and mechanism of acupuncture in patients with PD who have pain. PD patients with pain were divided into acupuncture group and control group. Nine patients completed acupuncture treatment; seven patients who received only an analgesic agent underwent resting-state functional magnetic resonance imaging (rs-fMRI) twice. fMRI was performed to evaluate the functional connectivity of the brain regions. After treatment, a decrease in total scores on the King's Parkinson's Disease Pain Scale (KPPS) and Unified Parkinson's Disease Rating Scale was observed in the acupuncture group (−46.2 and −21.6%, respectively). In the acupuncture group, increased connectivity was observed in four connections, one in the left hemisphere between the middle temporal gyrus (MTG) and precentral gyrus, and three in the right hemisphere between the postcentral gyrus and precentral gyrus, supramarginal gyrus and precentral gyrus, and MTG and insular cortex. A significant correlation was noted between the changes in functional connectivity and KPPS. The involved connection was between the left middle frontal gyrus and the right precentral gyrus (R = −0.698, P = 0.037). Acupuncture could relieve pain in PD patients by modulating brain regions related to both sensory-discriminative and emotional aspects. The present study might increase the confidence of users that acupuncture is an effective and safe analgesic tool that can relieve PD-related pain. [ABSTRACT FROM AUTHOR]

Background and Purpose: Non-motor symptoms of Parkinson disease (PD) have a strong negative impact on the health-related quality of life (QoL) of patients with PD. Sleep disturbance is an important non-motor symptom because of its high prevalence. However, previous studies investigating the determinants of sleep quality in patients with PD have revealed inconsistent results. Our study evaluated the correlations between sleep quality in patients with PD and disease-related variables, medications used depression, anxiety, and QoL and identified the determinants of sleep disturbance in people with PD in Taiwan. Methods: A total of 134 patients with PD were recruited from the outpatient clinic. We examined the correlations between the Parkinson disease sleep scale-2 (PDSS-2) scores and different variables, namely the Unified Parkinson Disease Rating Scale, Parkinson disease questionnaire, Beck Depression Inventory, and Beck Anxiety Inventory (BAI). Logistic regression analysis was used to assess the potential predictive variables for sleep quality in patients with PD. Results: Among our participants, 47.8% were classified as poor sleepers (PDSS-2 = 15–60). Correlation analysis demonstrated that poor sleepers exhibited longer disease durations, higher levodopa equivalent daily doses (LEDDs), higher PD severity, more depression and anxiety symptoms, poorer QoL, more frequent unemployed status, higher hypnotics use, higher dependency for activities of daily living, more motor impairments, and more therapy-related complications. Logistic regression revealed that the LEDD was a significant predictive factor of sleep quality. Conclusion: Poor sleepers constituted approximately half of our patients with PD. The participants experienced more favorable sleep if they were currently working. Increased PD duration, severity, depression or anxiety symptoms, and doses of dopaminergic therapy were significantly associated with poor sleep quality. Continued working, attempts to treat comorbid anxiety or depression, and avoidance of overdosage of dopaminergic treatments may improve sleep quality in patients with PD. [ABSTRACT FROM AUTHOR]

Nine autosomal dominant spinocerebellar ataxias (SCAs) are caused by an abnormal expansion of CAG trinucleotide repeats that encodes a polyglutamine (polyQ) tract within different genes. Accumulation of aggregated mutant proteins is a common feature of polyQ diseases, leading to progressive neuronal dysfunction and degeneration. SCA type 3 (SCA3), the most common form of SCA worldwide, is characterized by a CAG triplet expansion in chromosome 14q32.1 ATXN3 gene. As accumulation of the mutated polyQ protein is a possible initial event in the pathogenic cascade, clearance of aggregated protein by ubiquitin proteasome system (UPS) has been proposed to inhibit downstream detrimental events and suppress neuronal cell death. In this study, Chinese herbal medicine (CHM) extracts were studied for their proteasome-activating, polyQ aggregation-inhibitory and neuroprotective effects in GFPu and ATXN3/Q 7 5 -GFP 293/SH-SY5Y cells. Among the 14 tested extracts, 8 displayed increased proteasome activity, which was confirmed by 20S proteasome activity assay and analysis of ubiquitinated and fused GFP proteins in GFPu cells. All the eight extracts displayed good aggregation-inhibitory potential when tested in ATXN3/Q 7 5 -GFP 293 cells. Among them, neuroprotective effects of five selected extracts were shown by analyses of polyQ aggregation, neurite outgrowth, caspase 3 and proteasome activities, and ATXN3-GFP, ubiquitin, BCL2 and BAX protein levels in neuronal differentiated ATXN3/Q 7 5 -GFP SH-SY5Y cells. Finally, enhanced proteasome function, anti-oxidative activity and neuroprotection of catalpol, puerarin and daidzein (active constituents of Rehmannia glutinosa and Pueraria lobata) were demonstrated in GFPu and/or ATXN3/Q 7 5 -GFP 293/SH-SY5Y cells. This study may have therapeutic implication in polyQ-mediated disorders. [ABSTRACT FROM AUTHOR]

Previous genome-wide association studies in Caucasian populations suggest that genetic loci in amino acid catabolism may be associated with Parkinson's disease (PD). However, these genetic disease associations were limitedly reported in Asian populations. Herein, we investigated the effect of top three PD-associated genetic variants related to amino acid catabolism in Caucasians listed on the top risk loci identified by meta-analysis of genome-wide association studies in PDGene database, including aminocarboxymuconate-semialdehyde decarboxylase- (ACMSD-) transmembrane protein 163 (TMEM163) rs6430538, methylcrotonyl-CoA carboxylase 1 (MCCC1) rs12637471, and branched-chain ketoacid dehydrogenase kinase- (BCKDK-) syntaxin 1B (STX1B) rs14235, by genotyping 599 Taiwanese patients with PD and 598 age-matched control subjects. PD patients demonstrate similar allelic and genotypic frequencies in all tested genetic variants. These ethnic discrepancies of genetic variants suggest a distinct genetic background of amino acid catabolism between Taiwanese and Caucasian PD patients. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), associated with abnormal accumulation of amyloid-β (Aβ), is the most common cause of dementia among older people. A few studies have identified substantial AD biomarkers in blood but their results were inconsistent. Here we screened gene expression alterations on Aβ-GFP SH-SY5Y neuronal model for AD, and evaluated the findings on peripheral leukocytes from 78 patients with AD and 56 healthy controls. The therapeutic responses of identified biomarker candidates were further examined in Aβ-GFP SH-SY5Y neuronal and APP/PS1/Tau triple transgenic (3×Tg-AD) mouse models. Downregulation of apolipoprotein E (APOE) and tropomyosin receptor kinase A (TRKA) were detected in Aβ-GFP SH-SY5Y cells and validated by peripheral leukocytes from AD patients. Treatment with an in-house indole compound NC009-1 upregulated the expression of APOE and TRKA accompanied with improvement of neurite outgrowth in Aβ-GFP SH-SY5Y cells. NC009-1 further rescued the downregulated APOE and TRKA and reduced Aβ and tau levels in hippocampus and cortex, and ameliorated cognitive deficits in streptozocin-induced hyperglycemic 3×Tg-AD mice. These results suggest the role of APOE and TRKA as potential peripheral biomarkers in AD, and offer a new drug development target of AD treatment. Further studies of a large series of AD patients will be warranted to verify the findings and confirm the correlation between these markers and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to investigate the effects of a specific exercise (SE) training program focusing on balance and muscle strengthening, and a turning-based treadmill (TT) training program on cortical desynchronization and postural control in Parkinson’s disease (PD). The 18 patients with PD were recruited and randomly assigned to the SE group, TT training group or control exercise group and participated in 12 30 min training sessions focusing on balance and streng-thening, TT training, or general exercise training, respectively, followed by 10 min of over-ground walking in each session for 4 to 6 weeks. The outcomes included alpha event-related desynchronization (ERD), beta ERD, postural control ability indicated by postural instability and gait disorder (PIGD), the step/quick turn test (SQT), and the sensory organization test (SOT). All measurements were assessed at baseline and after training. The results (${n} =6$ for each group) showed that both the SE and TT groups had improved beta ERD, but not alpha ERD, in the Cz area, PIGD score, and turn sway/time in the SQT compared with the CE group. Furthermore, postural control ability was positively correlated with beta ERD in the Cz area. However, there was no significant correlation between SOT total score and alpha ERD in the Cz area. This paper showed that beta ERD in the central area and postural control can be improved with balance training, along with lower extremity muscle strengthening exercise and TT training, in patients with PD. Furthermore, improvement in beta ERD in the central area correlated with improvements in postural control ability. This trial was registered at http://www.anzctr.org.au/ (ACTRN12616000198426). [ABSTRACT FROM AUTHOR]

The pathogenesis of Parkinson’s disease (PD) remains to be elucidated. Metabolomic analysis has the potential to identify biochemical pathways and metabolic profiles that are involved in PD pathogenesis. Here, we performed a targeted metabolomics to quantify the plasma levels of 184 metabolites in a discovery cohort including 82 PD patients and 82 normal controls (NCs) and found two up-regulated (dopamine, putrescine/ornithine ratio) and four down-regulated (octadecadienylcarnitine C18:2, asymmetric dimethylarginine, tryptophan, and kynurenine (KYN)) metabolites in the plasma of PD patients. We then measured the plasma levels of a panel of metabolic products of KYN pathway in an independent validation cohort including 118 PD patients, 22 Huntington’s disease (HD) patients, and 37 NCs. Lower kynurenic acid (KA)/KYN ratio, higher quinolinic acid (QA) level, and QA/KA ratio were observed in PD patients compared to HD patients and NCs. PD patients at advanced stage (Hoehn-Yahr stage > 2) showed lower KA and KA/KYN ratio, as well as higher QA and QA/KA ratio compared to PD patients at early stage (Hoehn-Yahr stage ≤ 2) and NCs. Levels of KA and QA, as well as the ratios of KA/KYN and QA/KA between PD patients with and without psychiatric symptoms, dementia, or levodopa-induced dyskinesia in the advanced PD were similar. This metabolomic analyses demonstrate a number of plasma biomarker candidates for PD, suggesting a shift toward neurotoxic QA synthesis and away from neuroprotective KA production in KYN pathway. [ABSTRACT FROM AUTHOR]

Introduction: The coordination of swallowing and respiration is important for safety swallowing without aspiration. This coordination was affected in Parkinson disease (PD). A noninvasive assessment tool was used to investigate the effect of an easy-to-perform and device-free home-based orolingual exercise (OLE) program on swallowing and respiration coordination in patients with early-stage PD. Materials and Methods: This study had a quasi-experimental before-and-after exercise program design. Twenty six patients with early-stage PD who were aged 62.12 ± 8.52 years completed a 12-week home-based OLE program. A noninvasive assessment tool was used to evaluate swallowing and respiration. For each patient, we recorded and analyzed 15 swallows (3 repeats of 5 water boluses: 1, 3, 5, 10, and 20 mL) before and after the home-based OLE program. Oropharyngeal swallowing and its coordination with respiration were the outcome measures. The frequency of piecemeal deglutition, pre- and post-swallowing respiratory phase patterns, and parameters of oropharyngeal swallowing and respiratory signals (swallowing respiratory pause [SRP], onset latency [OL], total excursion time [TET], excursion time [ET], second deflexion, amplitude, and duration of submental sEMG activity, and amplitude of laryngeal excursion) were examined. Results: The rate of piecemeal deglutition decreased significantly when swallowing 10- and 20-mL water boluses after the program. In the 1-mL water bolus swallowing trial, the rate of protective pre- and post-swallowing respiratory phase patterns was significantly higher after the program. For the parameters of oropharyngeal swallowing and respiratory signals, only the amplitude of laryngeal excursion was significantly lower after the program. Moreover, the volume of the water bolus significantly affected the SRP and duration of submental sEMG when patients swallowed three small water bolus volumes (1, 3, and 5 mL). Conclusion: The home-based OLE program improved swallowing and its coordination with respiration in patients with early-stage PD, as revealed using a noninvasive method. This OLE program can serve as a home-based program to improve swallowing and respiration coordination in patients with early-stage PD. [ABSTRACT FROM AUTHOR]

Background: Akinetic mutism has often been used as the predictor of sporadic Creutzfeldt-Jacob disease (sCJD) endpoints, but it may be difficult for general physcians to assess. Nasogastric (NG) tube insertion is indicated for many neurodegenerative diseases with a clinical course of swallowing failure, and can be more easily identified than akinetic mutism by general physicians. Therefore, the aim of this study was to identify whether there are predictive factors for early initiation of artificial feeding in patients with sCJD who require enteral nutrition due to swallowing failure. Methods: We retrospectively reviewed the medical records of all patients diagnosed with probable sCJD who were admitted to the neurology ward at a medical center in Taiwan from January 2002 to July 2017. We used Pearson's chi-squared test to detect the correlation of initial symptoms, neurological signs, brain magnetic resonance imaging (MRI), electroencephalography (EEG), and increased levels of 14-3-3 protein in cerebrospinal fluid (CSF) analysis. The Cox proportional hazards model was used to detect prognostic factors for early initiation of NG tube insertion in sCJD patients. Results: The onset age ranged from 51 to 83 years, and mostly ranged from 60 to 79 years. Akinetic mutism was correlated with pyramidal tract signs, myoclonus, and extrapyramidal signs. Furthermore, myoclonus was revealed to be associated with pyramidal tract signs. Multivariate Cox regression analysis showed that myoclonus and elevated CSF levels of 14-3-3 protein are predictive of early NG insertion. Conclusions: Increased levels of 14-3-3 protein in CSF and the presence of myoclonus at diagnosis are predictive of early swallowing difficulty and indicate rapid deterioration in probable sCJD. In addition to akinetic mutism, early initiation of artificial feeding can be used to predict early deterioration in sCJD. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease (HD), caused by expansion of a polyglutamine tract within HUNTINGTIN (HTT) protein, is an autosomal dominant neurodegenerative disease associated with a progressive neurodegeneration of striatum and cerebral cortex. Although a few studies have identified substantial microRNA (miRNA) alterations in central nervous tissues from HD patients, it will be more accessible to employ these molecular changes in peripheral tissues as biomarkers for HD.Methods: We examined the expression levels of 13 miRNAs (miR-1, mirR-9, miR-9*, miR-10b, miR-29a, miR-29b, miR-124a, miR-132, miR-155, miR-196a, miR-196b, miR-330 and miR-615), 10 of which previously demonstrated alterations and 3 of which are potential regulators of differentially-expressed genes in brains of HD patients, in the peripheral leukocytes of 36 HD patients, 8 pre-symptomatic HD carriers and 28 healthy controls.Results: We found expression levels of miR-9* was significantly lower in HD patients compared with those in healthy controls, while other miRNAs did not show significant difference between these two groups. However, there was no significant correlation between Unified Huntington's Disease Rating Scales (UHDRS) and levels of miR-9* in peripheral leukocytes of HD patients.Conclusion: Our findings indicate the potential of miR-9* in peripheral leukocyte as a signature of neurodegeneration in HD patients. [ABSTRACT FROM AUTHOR]

Background Neurofibrillary tangles formed from tau misfolding have long been considered one of the pathological hallmarks of Alzheimer's disease ( AD). The misfolding of tau in AD correlates with the clinical progression of AD and inhibition or reversal of tau misfolding may protect the affected neurons. Methods We generated 293 and SH- SY5Y cells expressing DsRed-tagged pro-aggregation mutant of repeat domain of tau (ΔK280 tau RD) to test indole/indolylquinoline derivatives for reducing tau misfolding and neuroprotection. Results Four of the 10 derivatives tested displayed good misfolding-inhibitory effects on Tet-On 293 cells. Among them, NC009-1 and NC009-7 enhanced heat-shock 27 kDa protein 1 ( HSPB1) expression to increase ∆K280 tau RD-DsRed solubility and promoted neurite outgrowth in Tet-On SH- SY5Y cells. Knockdown of HSPB1 resulted in decreased ∆K280 tau RD-DsRed solubility and reduced neurite outgrowth, which were rescued by addition of NC009-1/ NC009-7. Treatment with indole/indolylquinoline derivatives also improved neuronal cell viability and neurite outgrowth in mouse hippocampal primary culture under tau cytotoxicity. Conclusion Our results demonstrate how indole/indolylquinoline derivatives are likely to work in tau misfolding reduction, providing insight into the possible working mechanism of indole and indolylquinoline derivatives in AD treatment. [ABSTRACT FROM AUTHOR]

Background Given the importance of ethnic differences in the evaluation of various aspects of symptoms in patients with Parkinson's disease ( PD), we present the formal procedure for completing the traditional Chinese translation of the International and Parkinson and Movement Disorder Society/ UPDRS ( MDS- UPDRS) and highlight the discrepancy in nonmotor symptoms ( NMS) between patients in Eastern and Western countries. Methods A total of 350 native Chinese-speaking PD patients were recruited from multiple hospitals in Eastern countries; they completed the MDS- UPDRS. The translation process was executed and factor analysis was performed to determine the structure of the scale. Chi-squared and t tests were used to compare frequency and severity of PD symptoms between the Chinese-speaking and English-speaking groups (n = 876). Results NMS and motor symptoms were more severe in the Western population (Part I: t(1205) = 5.36, P < 0.0001; and Part III: t(1205) = 7.64, P < 0.0001); however, the prevalence of cognitive dysfunction and impairments in activities of daily living were more frequent in the Eastern patients. The comparative fit index was 0.93 or greater, and the exploratory factor analysis revealed compatible results between the translated scale and the original version. Conclusion The traditional Chinese version of the MDS- UPDRS can be designated as an official translation of the original scale, and it is now available for use. Moreover, NMS in PD constitute a major issue worldwide, and the pattern of NMS among the Chinese population is more marked in terms of cognition-based symptoms and activities of daily living. [ABSTRACT FROM AUTHOR]

Huntington’s disease (HD) is a neurodegenerative disorder caused by the huntingtin (HTT) gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT) exists in the liver and causes urea cycle deficiency. A low protein diet (17%) restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories) than in mice (~22%). We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein) for 5 days, followed by a high protein diet (HPD, 26.3% protein) for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington’s Disease Rating Scale (UHDRS). The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378) in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression. [ABSTRACT FROM AUTHOR]