Dzamko, N;
Gysbers, AM;
Bandopadhyay, R;
Bolliger, MF;
Uchino, A;
Zhao, Y;
Takao, M;
... Halliday, GM; + view all
(2016)
LRRK2 Levels and Phosphorylation in Parkinson's Disease Brain and Cases With Restricted Lewy Bodies.
Movement Disorders
, 32
(3)
pp. 423-432.
10.1002/mds.26892.
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Abstract
Background: 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. Objectives: 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. Methods: LRRK2 and its phosphorylation were measured by immunoblot in brain regions differentially affected in Parkinson's disease (n = 30) as well as subjects with Lewy bodies restricted to the periphery and lower brain stem (n = 25) and matched controls without pathology (n = 25). Results: 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. Conclusions: 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. © 2016 International Parkinson and Movement Disorder Society
| Type: | Article |
|---|---|
| Title: | LRRK2 Levels and Phosphorylation in Parkinson's Disease Brain and Cases With Restricted Lewy Bodies |
| DOI: | 10.1002/mds.26892 |
| Publisher version: | https://doi.org/10.1002/mds.26892 |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, brain, alpha-synuclein, Parkinson's disease, Lewy body, phosphorylation, RICH REPEAT KINASE-2, 14-3-3 BINDING, CYTOPLASMIC LOCALIZATION, ALPHA-SYNUCLEIN, MUTATIONS, EXPRESSION, DEPHOSPHORYLATION, ASSOCIATION, INHIBITION, INCREASES |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10048721 |
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