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The autophagy process recycles dysfunctional cellular components and protein aggregates by sequestering them in autophagosomes directed to lysosomes for enzymatic degradation. A basal level of autophagy is essential for skeletal muscle maintenance. Increased autophagy occurs in several forms of muscular dystrophy and in the merosin-deficient congenital muscular dystrophy 1A mouse model (dy3k/dy3k) lacking the laminin-α2 chain. This pilot study aimed to compare autophagy marker expression and autophagosomes presence using light and electron microscopes and western blotting in diagnostic muscle biopsies from newborns affected by different congenital muscular myopathies and dystrophies. Morphological examination showed dystrophic muscle features, predominance of type 2A myofibers, accumulation of autophagosomes in the subsarcolemmal areas, increased number of autophagosomes overexpressing LC3b, Beclin-1 and ATG5, in the merosin-deficient newborn suggesting an increased autophagy. In Duchenne muscular dystrophy, nemaline myopathy, and spinal muscular atrophy the predominant accumulation of p62+ puncta rather suggests an autophagy impairment. [ABSTRACT FROM AUTHOR] more...

Background: Brain atrophy is a known marker of irreversible tissue damage in multiple sclerosis (MS). Cerebrospinal fluid (CSF) osteopontin (OPN) and neurofilament light chain (NF-L) have been proposed as candidate surrogate markers of inflammatory and neurodegenerative processes in MS. Objective: To evaluate the relationship between CSF NF-L and OPN levels and brain grey and white matter volumes in patients with clinically isolated syndrome (CIS) suggestive of MS. Methods: A total of 41 CIS patients and 30 neurological controls (NCs) were included. CSF NF-L and OPN were measured by commercial ELISA. Measures of brain volume (normalized brain volume (NBV), normalized grey matter volume (NGV), peripheral grey matter volume (PGV), normalized white matter volume (WMV), and ventricular volume) were obtained by SIENAX. Corpus callosum index (CCI) was calculated. Brain volumes were categorized into ‘high’ and ‘low’ according to the median value. Results: CSF NF-L and OPN levels were higher in CIS patients in comparison with NCs. CIS patients with ‘low’ TGV, PGV, and TBV showed higher CSF NF-L levels than CIS patients with ‘high’ brain volumes. TGV and PGV correlated inversely with NF-L levels, whereas CCI was inversely related to OPN levels. CSF NF-L was the only independent predictor of TGV and PGV. Conclusion: CSF NF-L tracks mainly grey matter damage in patients with CIS suggestive of MS. [ABSTRACT FROM AUTHOR] more...

Serum levels of N-acetyl-aspartate (NAA) may be considered a useful marker of neuronal functioning. We aimed to measure serum NAA in cohorts of migraine and tension-type headache patients versus controls, performing correlations with main clinical features. A total of 147 migraine patients (including migraine without aura, with aura and chronic migraine), 65 tension-type headache (including chronic and frequent episodic tension-type headache) and 34 sex- and age-matched controls were selected. Serum was stored at −80 °C. Quantification of NAA was achieved by the standard addition approach and analysis was performed with liquid-chromatography-mass-spectrometry (LC/MS) technique. The NAA levels were significantly decreased in migraine group (0.065 ± 0.019 mol/L), compared with both tension-type headache patients (0.078 ± 0.016 mol/L) and controls (0.085 ± 0.013 mol/L). Control subjects were significantly different from migraine with and without aura and chronic migraine, who differed significantly from episodic and chronic tension-type headache. Migraine with aura patients showed lower NAA levels when compared to all the other headache subtypes, including migraine without aura and chronic migraine. In the migraine group, no significant correlation was found between NAA serum levels, and headache frequency, allodynia and interval from the last and the next attack. The low NAA in the serum may be a sign of neuronal dysfunction predisposing to migraine, probably based on reduced mitochondria function. [ABSTRACT FROM AUTHOR] more...

Multiple sclerosis (MS) is a complex inflammatory and neurodegenerative chronic disease that involves the immune and central nervous systems (CNS). The pathogenesis involves the loss of blood–brain barrier integrity, resulting in the invasion of lymphocytes into the CNS with consequent tissue damage. The MS etiology is probably a combination of immunological, genetic, and environmental factors. It has been proposed that T lymphocytes have a main role in the onset and propagation of MS, leading to the inflammation of white matter and myelin sheath destruction. Cyclic AMP (cAMP), mitochondrial dysfunction, and oxidative stress exert a role in the alteration of T lymphocytes homeostasis and are involved in the apoptosis resistance of immune cells with the consequent development of autoimmune diseases. The defective apoptosis of autoreactive lymphocytes in patients with MS, allows these cells to perpetuate, within the CNS, a continuous cycle of inflammation. In this review, we discuss the involvement in MS of cAMP pathway, mitochondria, reactive oxygen species (ROS), apoptosis, and their interaction in the alteration of T lymphocytes homeostasis. In addition, we discuss a series of nutraceutical compounds that could influence these aspects. [ABSTRACT FROM AUTHOR] more...

Background: Plasma neurofilament light chain (NFL) has been measured as a biomarker of neuronal damage in various neurological disorders. Elevated tau and β-amyloid levels have been found in patients with fibromyalgia (FM). The aim of the present study was to compare plasma neurofilament levels in fibromyalgia patients with normal controls and to investigate the correlation with clinical features and cognitive tests., Methods: Plasma NFL levels were assessed in 33 FM patients and compared with 22 age-matched controls. All patients were also assessed with clinical scales examining fibromyalgia disability, sleep quality and duration, fatigue, anxiety, and depression, and a neuropsychological battery examining executive function, verbal short-term memory, and working memory, as well as attentional executive function and selective attention, interference sensitivity, and inhibition of automatic responses., Results: NFL levels were higher in FM patients (controls 6.19± 1.92; FM 17.28± 15.94 pg/mL ANOVA p 0.002). Working memory was the most impaired cognitive function significantly correlated with high NFL scores (Pearson p 0.034). Short sleep times also correlated with higher NFL scores (Pearson p 0.02) and poorer working memory performance (Pearson p 0.02). No correlation was found with indices of disease severity and duration., Conclusions: Plasma NFL levels are elevated in fibromyalgia patients, suggesting neuronal damage and correlating with a slight decrease in working memory and short sleep duration., Significance Statement: Plasma neurofilament levels are elevated in patients with fibromyalgia, regardless of disease severity and duration. Neurofilament levels are higher in patients with mild working memory impairment and sleep disorders. Subgroups of patients with primary neuronal damage phenomena could be individualized for prospective evaluation with regard to the possible development of cognitive decline and sleep disturbances, which would justify a tailored therapeutic approach., (© 2024 European Pain Federation ‐ EFIC ®.) more...

Background: Brain atrophy is a known marker of irreversible tissue damage in multiple sclerosis (MS). Cerebrospinal fluid (CSF) osteopontin (OPN) and neurofilament light chain (NF-L) have been proposed as candidate surrogate markers of inflammatory and neurodegenerative processes in MS., Objective: To evaluate the relationship between CSF NF-L and OPN levels and brain grey and white matter volumes in patients with clinically isolated syndrome (CIS) suggestive of MS., Methods: A total of 41 CIS patients and 30 neurological controls (NCs) were included. CSF NF-L and OPN were measured by commercial ELISA. Measures of brain volume (normalized brain volume (NBV), normalized grey matter volume (NGV), peripheral grey matter volume (PGV), normalized white matter volume (WMV), and ventricular volume) were obtained by SIENAX. Corpus callosum index (CCI) was calculated. Brain volumes were categorized into 'high' and 'low' according to the median value., Results: CSF NF-L and OPN levels were higher in CIS patients in comparison with NCs. CIS patients with 'low' TGV, PGV, and TBV showed higher CSF NF-L levels than CIS patients with 'high' brain volumes. TGV and PGV correlated inversely with NF-L levels, whereas CCI was inversely related to OPN levels. CSF NF-L was the only independent predictor of TGV and PGV., Conclusion: CSF NF-L tracks mainly grey matter damage in patients with CIS suggestive of MS. more...