The emerging role of LRRK2 in tauopathies
Author(s) -
Susanne Herbst,
Patrick A. Lewis,
Huw R. Morris
Publication year - 2022
Publication title -
clinical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.91
H-Index - 138
eISSN - 1470-8736
pISSN - 0143-5221
DOI - 10.1042/cs20220067
Subject(s) - lrrk2 , progressive supranuclear palsy , neuroscience , parkinson's disease , exocytosis , lewy body , endocytosis , neurite , disease , neurodegeneration , medicine , biology , tauopathy , pathology , genetics , receptor , in vitro , secretion
Parkinson's disease (PD) is conventionally described as an α-synuclein aggregation disorder, defined by Lewy bodies and neurites, and mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common autosomal dominant cause of PD. However, LRRK2 mutations may be associated with diverse pathologies in patients with Parkinson's syndrome including tau pathology resembling progressive supranuclear palsy (PSP). The recent discovery that variation at the LRRK2 locus is associated with the progression of PSP highlights the potential importance of LRRK2 in tauopathies. Here, we review the emerging evidence and discuss the potential impact of LRRK2 dysfunction on tau aggregation, lysosomal function, and endocytosis and exocytosis.
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