Journal
PARKINSONISM & RELATED DISORDERS
Volume 18, Issue 7, Pages 819-823Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2012.03.024
Keywords
LRRK2; I2020T mutation; Pathology; Tau; PARK8
Categories
Funding
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for Promotion of Science
- Takeda Science Foundation
- Mitsui Life Social Welfare Foundation
- Tokyo Metropolitan Organization for Medical Research
- core research for evolutional science and technology in the Japan Science and Technology
- Grants-in-Aid for Scientific Research [22500325, 22240039] Funding Source: KAKEN
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Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of autosornal-dominant familial Parkinson's disease (FPD). The variable pathological feature:3 of LRRK2-linked FPD include Lewy bodies, degeneration of anterior horn cells associated with axonal spheroids, neurofibrillary tangles (NFTs) and TAR DNA-binding protein of 43 kDa (TDP-43) positive inclusion bodies. Furthermore, abnormal hyperphosphorylation of microtubule associated protein tau, in part generated by catalysis of protein kinases, has been reported to be involved in progressive neurodegeneration in a number of diseases, including FPD. Thus, we examined six patients carrying the LRRK2 I2020T mutation, a pathogenic mutation associated with PARKS, and found abnormal tau phosphorylation depositions in the brainstem. Additionally, we found LRRK2 I2020T enhanced tau phosphorylation in cultured cells co-expressing LRRK2-I2020T and 3 or 4-repeated tau. This is the first report describing the relationship between hyperphosphorylation of tau and LRRK2 I2020T. (C) 2012 Elsevier Ltd. All rights reserved.
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