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Neurofilaments are structural proteins found in the cytoplasm of neurons, particularly in axons, providing structural support and stability to the axon. They consist of multiple subunits, including NF-H, NF-M, and NF-L, which form long filaments along the axon's length. Neurofilaments are crucial for maintaining the shape and integrity of neurons, promoting axonal transport, and regulating neuronal function. They are part of the intermediate filament (IF) family, which has approximately 70 tissue-specific genes. This diversity allows for a customizable cytoplasmic meshwork, adapting to the unique structural demands of different tissues and cell types. Neurofilament proteins show increased levels in both cerebrospinal fluid (CSF) and blood after neuroaxonal damage, indicating injury regardless of the underlying etiology. Precise measurement and long-term monitoring of damage are necessary for determining prognosis, assessing disease activity, tracking therapeutic responses, and creating treatments. These investigations contribute to our understanding of the importance of proper NF composition in fundamental neuronal processes and have implications for neurological disorders associated with NF abnormalities along with its alteration in different animal and human models. Here in this review, we have highlighted various neurological disorders such as Alzheimer's, Parkinson's, Huntington's, Dementia, and paved the way to use neurofilament as a marker in managing neurological disorders. [ABSTRACT FROM AUTHOR]

Neurodegenerative and neuropsychiatric disorders are two broad categories of neurological disorders characterized by progressive impairments in movement and cognitive functions within the central and peripheral nervous systems, and have emerged as a significant cause of mortality. Oxidative stress, neuroinflammation, and neurotransmitter imbalances are recognized as prominent pathogenic factors contributing to cognitive deficits and neurobehavioral anomalies. Consequently, preventing neurodegenerative and neuropsychiatric diseases has surfaced as a pivotal challenge in contemporary public health. This review explores the investigation of neurodegenerative and neuropsychiatric disorders using both synthetic and natural bioactive compounds. A central focus lies on melatonin, a neuroregulatory hormone secreted by the pineal gland in response to light-dark cycles. Melatonin, an amphiphilic molecule, assumes multifaceted roles, including scavenging free radicals, modulating energy metabolism, and synchronizing circadian rhythms. Noteworthy for its robust antioxidant and antiapoptotic properties, melatonin exhibits diverse neuroprotective effects. The inherent attributes of melatonin position it as a potential key player in the pathophysiology of neurological disorders. Preclinical and clinical studies have demonstrated melatonin's efficacy in alleviating neuropathological symptoms across neurodegenerative and neuropsychiatric conditions (depression, schizophrenia, bipolar disorder, and autism spectrum disorder). The documented neuroprotective prowess of melatonin introduces novel therapeutic avenues for addressing neurodegenerative and psychiatric disorders. This comprehensive review encompasses many of melatonin's applications in treating diverse brain disorders. Despite the strides made, realizing melatonin's full neuroprotective potential necessitates further rigorous clinical investigations. By unravelling the extended neuroprotective benefits of melatonin, future studies promise to deepen our understanding and augment the therapeutic implications against neurological deficits. [ABSTRACT FROM AUTHOR]

The smoothened sonic hedgehog (Smo-Shh) pathway is one mechanism that influences neurogenesis, including brain cell differentiation and development during childhood. Shh signaling dysregulation leads to decreased target gene transcription, which contributes to increased neuronal excitation, apoptosis, and neurodegeneration, eventually leading to neurological deficits. Neuropsychiatric disorders such as OCD and related neurological dysfunctions are characterized by neurotransmitter imbalance, neuroinflammation, oxidative stress, and impaired neurogenesis, disturbing the cortico-striato-thalamo-cortical (CSTC) link neuronal network. Despite the availability of several treatments, such as selective serotonin reuptake inhibitors, some individuals may not benefit much from them. Several trials on the use of antipsychotics in the treatment of OCD have also produced inadequate findings. This evidence-based review focuses on a potential pharmacological approach to alleviating OCD and associated neuronal deficits by preventing neurochemical alterations, in which sonic hedgehog activators are neuroprotective, lowering neuronal damage while increasing neuronal maintenance and survival. As a result, stimulating SMO-Shh via its potential activators may have neuroprotective effects on neurological impairment associated with OCD. This review investigates the link between SMO-Shh signaling and the neurochemical abnormalities associated with the progression of OCD and associated neurological dysfunctions. Role of Smo-Shh signaling in serotonergic neurogenesis and in maintaining their neuronal identity. The Shh ligand activates two main transcriptional factors known as Foxa2 and Nkx2.2, which again activates another transcriptional factor, GATA (GATA2 and GATA3), in post mitotic precursor cells of serotonergic neurons—following increased expression of Pet-1 and Lmx1b after GATA regulates the expression of many serotonergic enzymes such as TPH2, SERT, VMAT, slc6a4, Htr1a, Htr1b (Serotonin receptor enzymes), and MAO that regulate and control the release of serotonin and maintain their neuronal identity after their maturation. Abbreviation: Foxa2: Forkhead box; GATA: Globin transcription factor; Lmx1b: LIM homeobox transcription factor 1 beta; TPH2: Tryptophan hydroxylase 2; Htr1a: Serotonin receptor 1a; Htr1b: Serotonin receptor 1b; SERT: Serotonin transporter; VMAT: Vesicular monoamine transporter; MAO: Monoamine oxidase [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is distinguished by a triple repeat of CAG in exon 1, an increase in poly Q in the Htt gene, and a loss of GABAergic medium spiny neurons (MSN) in the striatum and white matter of the cortex. Mitochondrial ETC-complex dysfunctions are involved in the pathogenesis of HD, including neuronal energy loss, synaptic neurotrophic decline, neuronal inflammation, apoptosis, and grey and white matter destruction. A previous study has demonstrated that beta Boswellic acid (β-BA), a naturally occurring phytochemical, has several neuroprotective properties that can reduce pathogenic factors associated with various neurological disorders. The current investigation aimed to investigate the neuroprotective potential of β-BA at oral doses of 5, 10, and 15 mg/kg alone, as well as in conjunction with the potent antioxidant vitamin E (8 mg/kg, orally) in 3-NP-induced experimental HD rats. Adult Wistar rats were separated into seven groups, and 3-NP, at a dose of 10 mg/kg, was orally administered to each group of adult Wistar rats beginning on day 1 and continuing through day 14. The neurotoxin 3-NP induces neurodegenerative, g, neurochemical, and pathological alterations in experimental animals. Continuous injection of 3-NP, according to our results, aggravated HD symptoms by suppressing ETC-complex-II, succinate dehydrogenase activity, and neurochemical alterations. β-BA, when taken with vitamin E, improved behavioural dysfunctions such as neuromuscular and motor impairments, as well as memory and cognitive abnormalities. Pharmacological treatments with β-BA improved and restored ETC complexes enzymes I, II, and V levels in brain homogenates. β-BA treatment also restored neurotransmitter levels in the brain while lowering inflammatory cytokines and oxidative stress biomarkers. β-BA's neuroprotective potential in reducing neuronal death was supported by histopathological findings in the striatum and cortex. As a result, the findings of this research contributed to a better understanding of the potential role of natural phytochemicals β-BA in preventing neurological illnesses such as HD. [ABSTRACT FROM AUTHOR]

Background: Almost 50% of the Nepali health budget is made up of international aid. International Non-Governmental Organizations working in the field of health are able to channel their funds directly to grass root level. During a 2010 conference, the Secretary of Population stated that the government has full knowledge and control over all funds and projects coming to Nepal. However, there are no documents to support this. The study aims to assess government and partner perceptions on whether Government of Nepal currently has full knowledge of contributions of international aid organizations and International Non-Governmental Organizations to health in Nepal and to assess if the government is able to control all foreign contributions to fit the objectives of Second Long Term Health Plan (1997-2017). Methods: A qualitative study was performed along with available literature review. Judgmental and snowball sampling led to 26 in depth interviews with key informants from the government, External Development Partners and International Non-Governmental Organizations. Results were triangulated based on source of data. Representatives of the Department of Health Services declined to be interviewed. Data collection was done until researchers felt data saturation had been reached with each group of key informants. Results: While Ministry of Health and Population leads the sector wide approach that aims to integrate all donor and International Non-Governmental Organization contributions to health and direct them to the government's priority areas, questions were raised around its capacity to do so. Similarly, informants questioned the extent to which Social Welfare Council was able to control all International Non-Governmental Organizations contributions. Political tumult, corruption in the government, lack of human resources in the government, lack of coordination between government bodies, convoluted bureaucracy, and unreliability of donor and International Non- Governmental Organization contributions were identified as the main reasons for difficulties in aid integration. Conclusions: Despite its commitment to coordinate and control development assistance to the health sector, and its leadership position of the Sector Wide Approach, complete knowledge and effective coordination of all international contributions remains a challenge and is hampered by issues within the government as well as among External Development Partners and International Non-Governmental Organizations. [ABSTRACT FROM AUTHOR]

Background: Almost 50% of the Nepali health budget is made up of international aid. International Non-Governmental Organizations working in the field of health are able to channel their funds directly to grass root level. During a 2010 conference, the Secretary of Population stated that the government has full knowledge and control over all funds and projects coming to Nepal. However, there are no documents to support this. The study aims to assess government and partner perceptions on whether Government of Nepal currently has full knowledge of contributions of international aid organizations and International Non-Governmental Organizations to health in Nepal and to assess if the government is able to control all foreign contributions to fit the objectives of Second Long Term Health Plan (1997-2017).Methods: A qualitative study was performed along with available literature review. Judgmental and snowball sampling led to 26 in depth interviews with key informants from the government, External Development Partners and International Non-Governmental Organizations. Results were triangulated based on source of data. Representatives of the Department of Health Services declined to be interviewed. Data collection was done until researchers felt data saturation had been reached with each group of key informants.Results: While Ministry of Health and Population leads the sector wide approach that aims to integrate all donor and International Non-Governmental Organization contributions to health and direct them to the government's priority areas, questions were raised around its capacity to do so. Similarly, informants questioned the extent to which Social Welfare Council was able to control all International Non-Governmental Organizations contributions. Political tumult, corruption in the government, lack of human resources in the government, lack of coordination between government bodies, convoluted bureaucracy, and unreliability of donor and International Non-Governmental Organization contributions were identified as the main reasons for difficulties in aid integration.Conclusions: Despite its commitment to coordinate and control development assistance to the health sector, and its leadership position of the Sector Wide Approach, complete knowledge and effective coordination of all international contributions remains a challenge and is hampered by issues within the government as well as among External Development Partners and International Non-Governmental Organizations. [ABSTRACT FROM AUTHOR]