Cerebellar lipid dysregulation in SCA3: A comparative study in patients and mice

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106827 - 106827

Published: Feb. 1, 2025

Spinocerebellar ataxia type 3 (SCA3) is the most common dominantly inherited and belongs to family of nine diseases caused by a polyglutamine expansion in disease-causing protein. In SCA3, ATXN3 causes neuron loss disease-vulnerable brain regions, resulting progressive coordination ultimately death. There are no disease-modifying or preventative treatments for this uniformly fatal disorder. Recent studies demonstrate prominent white matter atrophy microstructural alterations regions SCA3 patients mouse models. However, major constituent - lipids remains understudied SCA3. study, we conducted first unbiased investigation focusing on cerebellum postmortem Liquid chromatography-mass spectrometry uncovered widespread lipid reductions with Lipid downregulation was recapitulated early- mid-stage models including transgenic YACQ84 Knock-in Q300 mice. End-stage mice displayed reduction content, highlighting targets that could benefit from early therapeutic intervention. contrast, Atxn3-Knock-out showed mild upregulation, emphasizing toxic gain-of-function mechanism underlying We conclude significantly altered establish platform continued exploration disease through interactive data visualization websites. Pronounced myelin-enriched suggest dysregulation underlie This study establishes basis future work elucidating mechanistic, biomarker, potential

Language: Английский

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Genetic perspective on the synergistic connection between vesicular transport, lysosomal and mitochondrial pathways associated with Parkinson’s disease pathogenesis

Acta Neuropathologica Communications, Journal Year: 2020, Volume and Issue: 8(1)

Published: May 6, 2020

Abstract Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS) are symptomatically characterized by parkinsonism, with the latter presenting additionally a distinctive range of features. Although majority patients PD APS appear to be sporadic, genetic causes several rare monogenic variants were identified. The knowledge acquired from these factors indicated that defects in vesicular transport pathways, endo-lysosomal dysfunction, impaired autophagy-lysosomal protein organelle degradation α-synuclein aggregation mitochondrial dysfunction play key roles pathogenesis. Moreover, membrane dynamics increasingly recognized as player pathogenesis due lipid homeostasis alterations, associated lysosomal caused mutations genes. importance is strengthened both discoveries clinical epidemiology association between parkinsonism storage disorders (LSDs), disruption biogenesis or function. A synergistic coordination trafficking, mitochondria exist whereby genes encoding proteins primarily involved one pathway frequently other pathways secondary effect. accumulating observations suggest more complex inheritance patters familial exist, including oligogenic polygenic same interconnected further strengthening their connection. Here, we provide comprehensive overview functions transport, highlight functional evidence connection pathways.

Language: Английский

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The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

Nutrients, Journal Year: 2020, Volume and Issue: 12(2), P. 435 - 435

Published: Feb. 8, 2020

Neurodegenerative diseases are progressive of the nervous system that lead to neuron loss or functional disorders. require long-term, sometimes life-long pharmacological treatment, which increases risk adverse effects and a negative impact pharmaceuticals on patients' general condition. One main problems related treatment this type condition is limited ability deliver drugs brain due their poor solubility, low bioavailability, blood-brain barrier. Given above, one objectives contemporary scientific research focuses prevention neurodegenerative diseases. As disorders competence antioxidative marker in all type, primary prophylactics should entail use exogenous antioxidants, particularly ones can be used over extended periods, regardless patient's age, easily available, e.g., as part diet supplements. The paper analyzes significance oxidoreductive balance pathogenesis Based information published globally last 10 years, an analysis also provided with regard antioxidants functions respect

Language: Английский

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Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson’s Disease Severity

Frontiers in Aging Neuroscience, Journal Year: 2020, Volume and Issue: 12

Published: March 6, 2020

Aim: Oxidative stress and inflammation play critical roles in the neuropathogenesis of PD. We aimed to evaluate oxidative status by measuring serum superoxide dismutase (SOD) with lipoprotein cholesterol high-sensitivity C-reactive protein (hsCRP) respectively PD patients, explore their correlation disease severity. Methods: performed a cross-sectional study that included 204 patients age-matched healthy controls (HCs). Plasma levels SOD, hsCRP, total cholesterol, high-density (HDL-C) low-density (LDL-C) were measured. A series neuropsychological assessments rate severity Results: The plasma SOD (135.7 ± 20.14 vs. 147.2 24.34, P < 0.0001), HDL-C LDL-C significantly lower than those HCs; hsCRP level was remarkably increased compared HC (2.766 3.242 1.637 1.597, 0.0001). negatively correlated while positively HDL-C, patients. H&Y, UPDRS, UPDRS (I), (II), (III) scores, but MoCA MMSE scores. Besides, MoCA; MoCA, respectively. Conclusion: Our findings suggest along LDL-C, higher might be important markers assess better understanding may yield insights into pathogenesis

Language: Английский

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Physical Exercise-Induced Myokines in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5795 - 5795

Published: May 28, 2021

Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and amyotrophic lateral sclerosis (ALS), are disorders characterized by progressive degeneration of the nervous system. Currently, there is no disease-modifying treatments for most NDs. Meanwhile, numerous studies conducted on human animal models over past decades have showed that exercises had beneficial effects Inter-tissue communication myokine, a peptide produced secreted skeletal muscles during exercise, thought to be an important underlying mechanism advantages. Here, we reviewed about myokines regulated exercise NDs their mechanisms. Myokines could exert through variety regulatory mechanisms, including cell survival, neurogenesis, neuroinflammation, proteostasis, oxidative stress, protein modification. Studies exercise-induced expected provide novel strategy treating NDs, which adequate nowadays. To date, only few been investigated mechanisms involved in them infancy. Therefore, future needed discover more test

Language: Английский

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