Lack of α-synuclein gene mutations in families with autosomal dominant Parkinson's disease in Russia

2000 ◽  
Vol 247 (12) ◽  
pp. 968-969 ◽  
Author(s):  
S.N. Illarioshkin ◽  
I.A. Ivanova-Smolenskaya ◽  
E.D. Markova ◽  
T.B. Zagorovskaya ◽  
A. Brice
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Autosomal Dominant ◽  
Gene Mutations

scholarly journals Therapeutic Potential of α-Synuclein Evolvability for Autosomal Recessive Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jianshe Wei ◽  
Gilbert Ho ◽  
Yoshiki Takamatsu ◽  
Eliezer Masliah ◽  
Makoto Hashimoto
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Therapeutic Potential ◽  
Gene Mutations ◽  
Mitochondrial Alteration ◽  
Rational Therapy ◽  
Ubiquitin Proteasome ◽  
Dominant Genes

The majority of Parkinson’s disease (PD) is sporadic in elderly and is characterized by α-synuclein (αS) aggregation and other alterations involving mitochondria, ubiquitin-proteasome, and autophagy. The remaining are familial PD associated with gene mutations of either autosomal dominant or recessive inheritances. However, the former ones are similar to sporadic PD, and the latter ones are accompanied by impaired mitophagy during the reproductive stage. Since no radical therapies are available for PD, the objective of this paper is to discuss a mechanistic role for amyloidogenic evolvability, a putative physiological function of αS, among PD subtypes, and the potential relevance to therapy. Presumably, αS evolvability might benefit familial PD due to autosomal dominant genes and also sporadic PD during reproduction, which may manifest as neurodegenerative diseases through antagonistic pleiotropy mechanism in aging. Indeed, there are some reports describing that αS prevents apoptosis and mitochondrial alteration under the oxidative stress conditions, notwithstanding myriads of papers on the neuropathology of αS. Importantly, β-synuclein (βS), the nonamyloidogenic homologue of αS, might buffer against evolvability of αS protofibrils associated with neurotoxicity. Finally, it is intriguing to predict that increased αS evolvability through suppression of βS expression might protect against autosomal recessive PD. Collectively, further studies are warranted to better understand αS evolvability in PD pathogenesis, leading to rational therapy development.

A frequent gene mutation associated with autosomal dominant Parkinson's disease

The Lancet ◽  
2005 ◽  
Vol 365 (9457) ◽  
pp. 412-415 ◽  
Author(s):  
A DIFONZO ◽  
C ROHE ◽  
J FERREIRA ◽  
H CHIEN ◽  
L VACCA ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gene Mutation ◽  
Autosomal Dominant

scholarly journals Study of The Collagen Type VI Alpha 3 (COL6A3) Gene in Parkinson’s Disease

2021 ◽  
Author(s):  
Chong-Yao Jin ◽  
Ran Zheng ◽  
Zhi-Hao Lin ◽  
Nai-Jia Xue ◽  
Ying Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Collagen Type ◽  
Gene Mutations ◽  
Compound Heterozygous ◽  
Genetic Characteristics ◽  
Increased Risk ◽  
Collagen Type Vi ◽  
Chinese Cohort ◽  
Aggregate Burden

Abstract Background To date, the genetic contribution to Parkinson’s disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort. Methods We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of < 0.01; and 2) the variant being recognized as deleterious by at least 15 different in silico predicting tools. Finally, we tested the aggregate burden of COL6A3 on PD via SKAT-O analysis. Results First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified seven novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.03). Conclusion An increased aggregate burden of the COL6A3 gene was detected in patients with PD.

CHCHD2 gene mutations in familial and sporadic Parkinson's disease

2016 ◽  
Vol 38 ◽  
pp. 217.e9-217.e13 ◽  
Author(s):  
Chang-he Shi ◽  
Cheng-yuan Mao ◽  
Shu-yu Zhang ◽  
Jing Yang ◽  
Bo Song ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gene Mutations ◽  
Sporadic Parkinson’S Disease

Neuronal microtubules and proteins linked to Parkinson’s disease: a relevant interaction?

2019 ◽  
Vol 400 (9) ◽  
pp. 1099-1112 ◽  
Author(s):  
Alessandra M. Calogero ◽  
Samanta Mazzetti ◽  
Gianni Pezzoli ◽  
Graziella Cappelletti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Intracellular Trafficking ◽  
Gene Mutations ◽  
Neuronal Loss ◽  
Leucine Rich Repeat ◽  
Microtubule Cytoskeleton ◽  
Pathological Conditions ◽  
Toxin Exposure ◽  
Relevant Interaction

AbstractNeuronal microtubules are key determinants of cell morphology, differentiation, migration and polarity, and contribute to intracellular trafficking along axons and dendrites. Microtubules are strictly regulated and alterations in their dynamics can lead to catastrophic effects in the neuron. Indeed, the importance of the microtubule cytoskeleton in many human diseases is emerging. Remarkably, a growing body of evidence indicates that microtubule defects could be linked to Parkinson’s disease pathogenesis. Only a few of the causes of the progressive neuronal loss underlying this disorder have been identified. They include gene mutations and toxin exposure, but the trigger leading to neurodegeneration is still unknown. In this scenario, the evidence showing that mutated proteins in Parkinson’s disease are involved in the regulation of the microtubule cytoskeleton is intriguing. Here, we focus on α-Synuclein, Parkin and Leucine-rich repeat kinase 2 (LRRK2), the three main proteins linked to the familial forms of the disease. The aim is to dissect their interaction with tubulin and microtubules in both physiological and pathological conditions, in which these proteins are overexpressed, mutated or absent. We highlight the relevance of such an interaction and suggest that these proteins could trigger neurodegeneration via defective regulation of the microtubule cytoskeleton.

The G2019SLRRK2 Mutation in Autosomal Dominant European and North African Parkinson's Disease is Frequent and its Penetrance is Age-Dependant: LBS.003

Neurology ◽  
2005 ◽  
Vol 64 (10) ◽  
pp. 1826-1826 ◽  
Author(s):  
S. Lesage ◽  
P. Ibanez ◽  
E. Lohmann ◽  
Y. Agid ◽  
A. Durr ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Autosomal Dominant ◽  
North African
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