Pathogenesis of Parkinson’s Disease

Neurologic Clinics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Expanding our understanding of synucleinopathies: proteinopathy, proteinopenia, and lipidopathy

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

A possible consequence of the process protein aggregation in neurodegenerative diseases is depletion soluble species (proteinopenia), which may, at least some cases, reduce function/activity. This concept, often overlooked, may play a role synucleinopathies such as Parkinson's disease (PD), and dementia with Lewy bodies (DLB), where α‐synuclein (aSyn) known to accumulate insoluble inclusions. aSyn crossroads between cellular proteostasis lipidostasis networks and, therefore, we must be aware complexity face when try understand molecular basis synucleinopathies. Importantly, β‐glucocerebrosidase (GCase), sphingolipid hydrolase also strongly implicated PD DLB, are connected lipid biology quality control function. Thus, changes normal relationship these two proteins shift balance cell lead proteinopathy and/or proteinopenia, while affecting cells brain. pathological mechanisms that (a) loss‐of‐function, (b) gain‐of‐toxic function, (c) alterations need carefully analyzed integrated our study underpinnings mechanisms. Here, highlight implications form aSyn, GCase, discuss how state‐of‐the‐art ‘omics technologies’ could deployed assist clinical assessment

Language: Английский

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Human Endogenous Retrovirus K in Astrocytes Is Altered in Parkinson's Disease

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract Background Parkinson's disease (PD) is the most common neurodegenerative movement disease. Human endogenous retroviruses (HERVs) are proviral remnants of ancient retroviral infection germ cells that now constitute about 8% human genome. Under certain conditions, HERV genes activated and partake in process. However, virtually nothing known pathological relationship, if any, between PD. Objective The objectives this study were to unravel relationship retrovirus K (HERV‐K) PD, determine localization HERV‐K brain, whether levels altered PD brain blood, examine could serve as a biomarker for Methods In situ glial fibrillary acidic protein (GFAP) expression superior frontal fusiform cortices control analyzed using immunofluorescence confocal microscopy. load copy number blood measured by digital droplet polymerase chain reaction GFAP single‐molecule array. was relation Hoehn Yahr Scale Movement Disorder Society Unified Disease Rating Part III. Results predominantly expressed astrocytes colocalized with astrocytic GFAP, decreased both compared controls. Consistent this, controls correlated levels. inversely severity duration. Conclusions These findings suggest related astrocyte function progression, be neuroprotective. © 2025 Author(s). Disorders published Wiley Periodicals LLC on behalf International Parkinson Society.

Language: Английский

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Metabolomics in Parkinson’s Disease and Correlation with Disease State

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 208 - 208

Published: March 18, 2025

Changes in the level of metabolites, small molecules that are intermediates produced by metabolism or catabolism, associated with developing diseases. Metabolite signatures body fluids such as plasma, cerebrospinal fluid, urine, and saliva Parkinson’s disease. Here, we discuss alteration metabolites TCA cycle, pentose phosphate pathway, kynurenic network, redox system. We also summarize efforts many research groups to differentiate between metabolite profiles characterize PD motor progression dyskinesia, gait balance, non-motor symptoms depression cognitive decline. Understanding how changes lead may allow for identification individuals at earliest stage disease development new therapeutic strategies.

Language: Английский

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Application of Nanobiosensor Engineering in the Diagnosis of Neurodegenerative Disorders

Results in Engineering, Journal Year: 2024, Volume and Issue: 24, P. 102790 - 102790

Published: Sept. 5, 2024

Language: Английский

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Biomarker‐Based Approach to α‐Synucleinopathies: Lessons from Neuropathology

Movement Disorders, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

Language: Английский

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Parkinson’s Disease: Biomarkers for Diagnosis and Disease Progression

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12379 - 12379

Published: Nov. 18, 2024

Parkinson's disease (PD) is a progressive neurological that causes both motor and nonmotor symptoms. While our understanding of putative mechanisms has advanced significantly, it remains challenging to verify biomarkers with sufficient evidence for regular clinical use. Clinical symptoms are the primary basis diagnosing disease, which can be mild in early stages overlap other disorders. As result, testing medical records mostly relied upon diagnosis, posing substantial challenges during initial diagnosis continuous monitoring. Recent biochemical, neuroimaging, genetic have helped us understand pathophysiology disease. This comprehensive study focuses on these biomarkers, were chosen based their relevance, methodological excellence, contribution field. Biochemical including α-synuclein glial fibrillary acidic protein (GFAP), predict severity progression. The dopaminergic system widely used as neuroimaging biomarker diagnose PD. Numerous genes genome wide association (GWAS) sites been related development research SNCA gene leucine-rich repeat kinase 2 (LRRK2) shown promising results. By evaluating current studies, this review intends uncover gaps validation use, while also highlighting improvements. It emphasizes need dependable reproducible indicators improving PD prognosis. These may open up new avenues progression tracking, personalized treatment programs.

Language: Английский

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Exploring SERPINA3 as a neuroinflammatory modulator in Alzheimer’s disease with sex and regional brain variations

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(1)

Published: Jan. 4, 2025

Language: Английский

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G protein-coupled receptors: a golden key to the treasure-trove of neurodegenerative diseases

Clinical Nutrition, Journal Year: 2025, Volume and Issue: 46, P. 155 - 168

Published: Feb. 2, 2025

Language: Английский

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A perspective of persons with Parkinson's disease on the contribution of alpha-synuclein seed amplification assay biomarker to the diagnosis of Parkinson's disease

Journal of Parkinson s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

Alpha-synuclein is a normal protein, but misfolded forms in the cerebrospinal fluid can be detected using alpha-synuclein seed amplification assay (αSyn-SAA), potential biomarker for Parkinson's disease (PD). Some experts consider this ‘game changer’ redefining and reclassifying PD. In article, we, three individuals with PD, share our perspective on suitability of αSyn-SAA as basis new classification staging system We also discuss other biomarkers their relevance to those drawing research scientific background two authors. aim clarify complex media reports study findings PD community. argue that while identify presence pathology, it cannot explain underlying cause such pathology or predict progression Given varied biological pathways leading unified definition premature. Further needed before serve foundation defining disease. Although has its place, like DAT scan, should seen tool confirming diagnoses rather than them.

Language: Английский

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