{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:40:56Z","timestamp":1790505656519,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,12,2]],"date-time":"2016-12-02T00:00:00Z","timestamp":1480636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Disease Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Australia Foundation"},{"name":"National Health and Medical Research Council of Australia","award":["1079679"],"award-info":[{"award-number":["1079679"]}]},{"name":"Reta Lila Weston Trust"},{"DOI":"10.13039\/100013128","name":"Multiple System Atrophy Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013128","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Alzheimer's Research UK"},{"name":"CBD Solutions"},{"name":"Stichting Parkinson Fonds, Internationale Stichting Alzheimer onderzoek"},{"name":"ZonMW Memorabel Deltaplan Dementia"},{"name":"Queen Square Brain Bank"},{"name":"Reta Lila Weston Institute for Neurological Studies and the Medical Research Council UK"},{"name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:bold>Background<\/jats:bold>: Leucine rich repeat kinase 2 (LRRK2) is a promising target for the treatment of Parkinson's disease; however, little is known about the expression of LRRK2 in human brain and if\/how LRRK2 protein levels are altered in Parkinson's disease.<\/jats:p><jats:p><jats:bold>Objectives<\/jats:bold>: We measured the protein levels of LRRK2 as well as its phosphorylation on serines 910, 935, and 973 in the postmortem brain tissue of Parkinson's disease patients and aged controls with and without Lewy bodies.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>: LRRK2 and its phosphorylation were measured by immunoblot in brain regions differentially affected in Parkinson's disease (n\u2009=\u200930) as well as subjects with Lewy bodies restricted to the periphery and lower brain stem (n\u2009=\u200925) and matched controls without pathology (n\u2009=\u200925).<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>: LRRK2 levels were increased in cases with restricted Lewy bodies, with a 30% increase measured in the substantia nigra. In clinical Parkinson's disease, levels of LRRK2 negatively correlated to disease duration and were comparable with controls. LRRK2 phosphorylation, however, particularly at serine 935, was reduced with clinical Parkinson's disease with a 36% reduction measured in the substantia nigra.<\/jats:p><jats:p><jats:bold>Conclusions<\/jats:bold>: Our data show that LRRK2 phosphorylation is reduced with clinical PD, whereas LRRK2 expression is increased in early potential prodromal stages. These results contribute to a better understanding of the role of LRRK2 in idiopathic Parkinson's disease and may aid efforts aimed at therapeutically targeting the LRRK2 protein. \u00a9 2016 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.26892","type":"journal-article","created":{"date-parts":[[2016,12,2]],"date-time":"2016-12-02T07:42:42Z","timestamp":1480664562000},"page":"423-432","source":"Crossref","is-referenced-by-count":57,"title":["LRRK2 levels and phosphorylation in Parkinson's disease brain and cases with restricted Lewy bodies"],"prefix":"10.1002","volume":"32","author":[{"given":"Nicolas","family":"Dzamko","sequence":"first","affiliation":[{"name":"School of Medical Sciences University of New South Wales Kensington Australia"},{"name":"Neuroscience Research Australia Randwick Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Gysbers","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia Randwick Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Bandopadhyay","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank, UCL Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc F.","family":"Bolliger","sequence":"additional","affiliation":[{"name":"Parkinson's Institute and Clinical Center Sunnyvale California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Uchino","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Brain Bank for Aging Research Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Medical Sciences University of New South Wales Kensington Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Takao","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Brain Bank for Aging Research Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology Tokyo Japan"},{"name":"Department of Neurology Saitama Medical University, International Medical Centre Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Wauters","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank, UCL Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma D. 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