Identification of Targets from LRRK2 Rescue Phenotypes.


Journal

Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052

Informations de publication

Date de publication:
05 01 2021
Historique:
received: 08 12 2020
revised: 31 12 2020
accepted: 31 12 2020
entrez: 20 1 2021
pubmed: 21 1 2021
medline: 24 6 2021
Statut: epublish

Résumé

Parkinson's disease (PD) is an age-dependent neurodegenerative condition. Leucine-rich repeat kinase 2 (LRRK2) mutations are the most frequent cause of sporadic and autosomal dominant PD. The exact role of LRRK2 protective variants (R1398H, N551K) together with a pathogenic mutant (G2019S) in aging and neurodegeneration is unknown. We generated the following myc-tagged UAS-LRRK2 transgenic Drosophila: LRRK2 (WT), N551K, R1398H, G2019S single allele, and double-mutants (N551K/G2019S or R1398H/G2019S). The protective variants alone were able to suppress the phenotypic effects caused by the pathogenic LRRK2 mutation. Next, we conducted RNA-sequencing using mRNA isolated from dopaminergic neurons of these different groups of transgenic

Identifiants

pubmed: 33466414
pii: cells10010076
doi: 10.3390/cells10010076
pmc: PMC7824855
pii:
doi:

Substances chimiques

Drosophila Proteins 0
LRRK2 protein, human EC 2.7.11.1
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

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Auteurs

Joanne Toh (J)

Department of Research, National Neuroscience Institute, SGH Campus, Singapore 169856, Singapore.

Ling Ling Chua (LL)

Department of Research, National Neuroscience Institute, SGH Campus, Singapore 169856, Singapore.

Patrick Ho (P)

Department of Research, National Neuroscience Institute, SGH Campus, Singapore 169856, Singapore.

Edwin Sandanaraj (E)

Department of Research, National Neuroscience Institute, SGH Campus, Singapore 169856, Singapore.
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore 117609, Singapore.

Carol Tang (C)

Department of Research, National Neuroscience Institute, Singapore 308433, Singapore.
Duke NUS Medical School, Singapore 169857, Singapore.
Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore 169610, Singapore.

Hongyan Wang (H)

Neuroscience and Behavioral Disorders Program, Duke NUS Medical School, Singapore 169857, Singapore.
National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, Singapore.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.

Eng King Tan (EK)

Department of Neurology, National Neuroscience Institute Singapore, Singapore 308433, Singapore.
Department of Neurology, National Neuroscience Institute, SGH Campus, Singapore 169856, Singapore.

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Classifications MeSH