Premium
LRRK2 pathobiology in Parkinson's disease – virtual inclusion
Author(s) -
Martin Ian,
Kim Jungwoo Wren,
Dawson Valina L.,
Dawson Ted M.
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13549
Subject(s) - lrrk2 , missense mutation , parkinson's disease , protein kinase domain , kinase , disease , neuroscience , gtpase , bioinformatics , medicine , biology , mutation , microbiology and biotechnology , genetics , gene , mutant
Abstract A common cause of Parkinson disease are missense mutations in the leucine‐rich repeat kinase 2 (LRRK2) catalytic Roc‐COR domain, leading to a decrease in GTPase activity; and its kinase domain, leading to an increase in kinase activity and subsequent LRRK2 toxicity. Targeting LRRK2 with selective, brain‐permeable kinase inhibitors is a promising approach to reduce toxicity, and thus is a major goal of clinical development. Understanding the specific signaling cascades triggered by LRRK2 mutations will be key to this aim. This article is part of a special issue on Parkinson disease .