Parkinson's disease and α‐synuclein expression
TLDR
The clinical impact of α‐synuclein locus multiplications, and the implications that this has for Parkinson's disease pathogenesis are outlined; potential strategies for disease‐modifying therapies for this currently incurable disorder are discussed.Abstract:
Genetic studies of Parkinson's disease over the last decade or more have revolutionized our understanding of this condition. α-Synuclein was the first gene to be linked to Parkinson's disease, and is arguably the most important: the protein is the principal constituent of Lewy bodies, and variation at its locus is the major genetic risk factor for sporadic disease. Intriguingly, duplications and triplications of the locus, as well as point mutations, cause familial disease. Therefore, subtle alterations of α-synuclein expression can manifest with a dramatic phenotype. We outline the clinical impact of α-synuclein locus multiplications, and the implications that this has for Parkinson's disease pathogenesis. Finally, we discuss potential strategies for disease-modifying therapies for this currently incurable disorder.read more
Citations
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O1-7-4-1Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease
Wataru Satake,Ikuko Mizuta,Michiaki Kubo,Takahisa Kawaguchi,Tatsuhiko Tsunoda,Takeo Yoshikawa,Saburo Sakoda,Mitsutoshi Yamamoto,Nobutaka Hattori,Miho Murata,Yusuke Nakamura,Tatsushi Toda +11 more
TL;DR: Clinical and genetic information of 5 Japanese patients with Bardet-Biedl syndrome is summarized and it is found that rare liver fibrosis was detected in two patients, while only two patients had renal dysfunction, thought to be a universal symptom.
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Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression
Frank Soldner,Yonatan Stelzer,Chikdu S. Shivalila,Brian J. Abraham,Jeanne C. Latourelle,M. Inmaculada Barrasa,Johanna Goldmann,Richard H. Myers,Richard A. Young,Rudolf Jaenisch +9 more
TL;DR: This work establishes an experimental paradigm to functionally connect genetic variation with disease-relevant phenotypes by combining genome-wide epigenetic information with clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9 genome editing in human pluripotent stem cells.
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α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy?
Aoife Kiely,Yasmine T. Asi,Eleanna Kara,Patricia Limousin,Patricia Limousin,Helen Ling,Patrick A. Lewis,Patrick A. Lewis,Christos Proukakis,Niall Quinn,Andrew J. Lees,John Hardy,Tamas Revesz,Henry Houlden,Janice L. Holton +14 more
TL;DR: A British family with young-onset Parkinson’s disease and a G51D SNCA mutation that segregates with the disease and post-mortem brain examination of the proband revealed atrophy affecting frontal and temporal lobes, which could aid in understanding of α-synuclein biology and its impact on disease phenotype.
Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression
Frank Soldner,Yonatan Stelzer,Brian J. Abraham,Jeanne C. Latourelle,M. Inmaculada Barrasa,Johanna Goldmann,Richard H. Myers,Richard A. Young,Rudolf Jaenisch,Chikdu S. Shivalila +9 more
Journal ArticleDOI
MicroRNA-7 targets Nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson’s disease
Yan Zhou,Ming Lu,Ren-Hong Du,Chen Qiao,Chun-Yi Jiang,Ke-Zhong Zhang,Jian-Hua Ding,Gang Hu,Gang Hu,Gang Hu +9 more
TL;DR: This study provides a direct link between miR-7 and NLRP3 inflammasome-mediated neuroinflammation in the pathogenesis of PD and demonstrates for the first time that Nlrp3 is a target gene of microRNA-7 (miR- 7).
References
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