Genetic Architecture of Parkinson’s Disease

Biochemistry (Moscow), Год журнала: 2023, Номер 88(3), С. 417 - 433

Опубликована: Март 1, 2023

Abstract Year 2022 marks 25 years since the first mutation in familial autosomal dominant Parkinson’s disease was identified. Over years, our understanding of role genetic factors pathogenesis and idiopathic forms has expanded significantly – a number genes for form have been identified, DNA markers an increased risk developing its sporadic found. But, despite all success achieved, we are far from accurate assessment contribution and, even more so, epigenetic to development. The review summarizes information accumulated date on architecture formulates issues that need be addressed, which primarily related pathogenesis.

Язык: Английский

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The international cooperative Gaucher group (ICCG) Gaucher registry

Best Practice & Research Clinical Haematology, Год журнала: 2023, Номер 36(4), С. 101522 - 101522

Опубликована: Ноя. 1, 2023

Язык: Английский

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Genetics of Multiple System Atrophy and Progressive Supranuclear Palsy: A Systemized Review of the Literature

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5281 - 5281

Опубликована: Март 9, 2023

Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are uncommon multifactorial atypical Parkinsonian syndromes, expressed by various clinical features. MSA PSP commonly considered sporadic neurodegenerative disorders; however, our understanding is improving of their genetic framework. The purpose this study was to critically review the genetics involvement in pathogenesis. A systemized literature search PubMed MEDLINE performed up 1 January 2023. Narrative synthesis results undertaken. In total, 43 studies were analyzed. Although familial cases have been reported, hereditary nature could not be demonstrated. COQ2 mutations involved MSA, without being reproduced populations. terms cohort, synuclein alpha (SNCA) polymorphisms correlated with an elevated likelihood manifesting Caucasians, but a causal effect relationship Fifteen MAPT linked PSP. Leucine-rich repeat kinase 2 (LRRK2) infrequent monogenic mutation Dynactin subunit (DCTN1) may imitate phenotype. GWAS noted many risk loci (STX6 EIF2AK3), suggesting pathogenetic mechanisms related Despite limited evidence, it seems that influence susceptibility result pathologies. Further crucial elucidate pathogeneses PSP, which will support efforts develop novel drug options.

Язык: Английский

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Mitochondrial oxidant stress promotes α-synuclein aggregation and spreading in mice with mutated glucocerebrosidase

npj Parkinson s Disease, Год журнала: 2024, Номер 10(1)

Опубликована: Дек. 11, 2024

Abstract In this study, heterozygous expression of a common Parkinson-associated GBA1 variant, the L444P mutation, was found to exacerbate α-synuclein aggregation and spreading in mouse model Parkinson-like pathology targeting neurons medullary vagal system. These were also shown become more vulnerable oxidative nitrative stress after expression. The latter paralleled neuronal formation reactive oxygen species led pronounced accumulation nitrated α-synuclein. A causal relationship linked mutation-induced oxidative/nitrative enhanced that could indeed be rescued by overexpression mitochondrial superoxide dismutase 2. Further evidence supported key involvement mitochondria as sources well targets damage within L444P-expressing neurons. findings support conclusion vulnerability should considered an important mechanism predisposing conversion carriers mutations.

Язык: Английский

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

Movement Disorders, Год журнала: 2024, Номер unknown

Опубликована: Дек. 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.

Язык: Английский

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