Pathogenesis of Parkinson’s Disease

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

Published: Jan. 1, 2025

Language: Английский

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Intraparenchymal delivery of adeno-associated virus vectors for the gene therapy of neurological diseases

Expert Opinion on Biological Therapy, Journal Year: 2024, Volume and Issue: 24(8), P. 773 - 785

Published: July 27, 2024

In gene therapy with adeno-associated virus (AAV) vectors for diseases of the central nervous system, can be administered into blood vessels, cerebrospinal fluid space, or brain parenchyma. When transfer to a large area is required, first two methods are used, but in which local expected effective, directly

Language: Английский

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Organic solvents and neurodegenerative diseases: Exploring a possible link

Advances in neurotoxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Population-Specific Differences in Pathogenic Variants of Genes Associated with Monogenic Parkinson’s Disease

Genes, Journal Year: 2025, Volume and Issue: 16(4), P. 454 - 454

Published: April 15, 2025

Background: Parkinson’s disease (PD) is a genetically complex neurodegenerative disorder. Up to 15% of cases are considered monogenic. However, research on monogenic PD has largely focused populations European ancestry, leaving gaps in our understanding genetic variability other populations. This study addresses this gap by analysing the allele frequencies pathogenic and likely variants known genes across eight global populations, using data from gnomAD database. Methods: We compiled list 27 associated with Mendelian Online Inheritance Man (OMIM) database, identified ClinVar. then performed pairwise comparisons included Variants significant frequency differences were further assessed silico pathogenicity predictions. Results: 81 17 statistically between at least two GBA1 most prevalent among PD-related genes, followed PLA2G6, ATP13A2, VPS13C, PRKN. exhibited greatest frequencies, particularly NM_000157.4:c.1226A>G (p.Asn409Ser) variant. Additionally, we observed population-specific variants, such as NM_032409.3:c.1040T>C (p.Leu347Pro) variant PINK1, which was East Asian Conclusions: Our findings reveal substantial linked PD, emphasising need for broader studies beyond These insights have important implications research, screening, pathogenesis diverse

Language: Английский

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RISCO GENÉTICO PARA A DOENÇA DE PARKINSON: REVISÃO INTEGRATIVA DAS DESCOBERTAS ATUAIS

Published: May 20, 2025

A Doença de Parkinson (DP) é uma enfermidade neurodegenerativa multifatorial, cujas causas envolvem interações complexas entre predisposição genética, epigenética e fatores ambientais. Com o avanço da diversos genes têm sido associados à suscetibilidade progressão doença, como SNCA, LRRK2, GBA1 PINK1. Este estudo teve objetivo analisar os principais genéticos relacionados ao risco desenvolver DP. Trata-se revisão integrativa realizada nas bases dados PubMed, SciELO LILACS, com uso dos descritores “Genetic Predisposition to Disease” “Parkinson Disease”. Foram incluídos 13 estudos originais publicados nos últimos cinco anos, excluindo-se trabalhos modelos animais ou não disponíveis na íntegra. Os resultados apontam que a DP resulta interação variantes monogênicas poligênicas, influenciando diferentes manifestações clínicas. Fatores epigenéticos, regulação por miRNAs, ampliam compreensão doença abrem possibilidades terapêuticas emergentes, incluindo inibidores exossomos terapias celulares. Conclui-se integração tecnologias avançadas pode favorecer diagnósticos precoces tratamentos personalizados, embora persistam desafios técnicos éticos. continuidade das pesquisas fundamental para consolidar medicina precisão eficaz no manejo

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Recent advances in the genetics of Parkinson's disease in underrepresented populations

Current Opinion in Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: June 5, 2025

Purpose of review The aim this study is to highlight recent key developments in Parkinson's disease genetics research underrepresented populations, point out gaps related ethnic and geographical diversity, suggest future directions for increasing representation Recent findings Genome-wide association studies (GWAS) involving non-European ancestries have identified population-specific risk variants, even with relatively small sample sizes compared European GWAS. Polygenic scores derived from cohorts often fail generalize populations. Additionally, the prevalence variants genes, such as LRRK2 GBA1 , varies across Monogenic regions like African Latin America face significant challenges, including limited infrastructure underrepresentation genetic studies, hindering a comprehensive understanding disease's diversity. Summary Expanding include diverse populations essential enhance understanding, uncover novel therapeutic targets, ensure equitable access precision medicine. Addressing participation barriers investing development progress.

Language: Английский

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PSMF1variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 20, 2024

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes identification potential biomarkers therapeutic targets. Here, we identify

Language: Английский

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Parkinson's Disease, Diagnosis

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

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Targeting Protein Misfolding and Aggregation as a Therapeutic Perspective in Neurodegenerative Disorders

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12448 - 12448

Published: Nov. 20, 2024

The abnormal deposition and intercellular propagation of disease-specific protein play a central role in the pathogenesis many neurodegenerative disorders. Recent studies share common observation that formation oligomers subsequent pathological filaments is an essential step for disease. Synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) are diseases characterized by aggregation α-synucleinprotein neurons and/or oligodendrocytes (glial cytoplasmic inclusions), neuronal loss, astrogliosis. A similar mechanism Tau-dependent neurodegeneration major feature tauopathies, represented Alzheimer's (AD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), Pick's (PD). specific inhibition misfolding their interneuronal spreading represents promising therapeutic strategy against both pathology progression. most recent research focuses on finding potential applications targeting forms proteins responsible neurodegeneration. This review highlights mechanisms relevant to protein-dependent based disorders describes current approaches aggregation.

Language: Английский

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The RAB32 p.Ser71Arg Variant in Parkinsonisms: Insights from a Large Italian Cohort

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

Published: Dec. 31, 2024

Recently, RAB32 has been identified as possibly linked to Parkinson's disease. We studied the prevalence and clinical correlates of p.Ser71Arg variant in gene a large case series Italian patients with disease or atypical parkinsonism.

Language: Английский

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