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Abnormal Localizationof Leucine-RichRepeat Kinase 2 totheEndosomal-LysosomalCompartment in LewyBody Disease Shinji HigashiDarren J. MooreRyoko Yamamoto2009 год

Abnormal Localization of Leucine-Rich Repeat Kinase 2 to the Endosomal-Lysosomal Compartment in Lewy Body Disease
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Аннотация: Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common causes of both familial and sporadic forms of Parkinson disease and are also associated with diverse pathological alterations. The mechanisms whereby LRRK2 mutations cause these pathological phenotypes are unknown. We used immunohistochemistry with 3 distinct anti-LRRK2 antibodies to characterize the expression of LRRK2 in the brains of 21 subjects with various neurodegenerative disorders and 7 controls. The immunoreactivity of LRRK2 was localized in a subset of brainstem-type Lewy bodies (LBs) but not in cortical-type LBs, tau-positive inclusions, or TAR-DNA-binding protein-43-positive inclusions. The immunoreactivity of LRRK2 frequently appeared as enlarged granules or vacuoles within neurons of affected brain regions, including the substantia nigra, amygdala, and entorhinal cortex in patients with Parkinson disease or dementia with LBs. The volumes of LRRK2-positive granular structures in neurons of the entorhinal cortex were significantly increased in dementia with LBs brains compared with age-matched control brains (p < 0.05). Double immunolabeling demonstrated that these LRRK2-positive granular structures frequently colocalized with the late-endosomal marker Rab7B and occasionally with the lysosomal marker, the lysosomal-associated membrane protein 2. These results suggest that LRRK2 normally localizes to the endosomal-lysosomal compartment within morphologically altered neurons in neurodegenerative diseases, particularly in the brains of patients with LB diseases.
Год издания: 2009
Авторы: Shinji Higashi, Darren J. Moore, Ryoko Yamamoto, Michiko Minegishi, Kiyoshi Sato, Takashi Togo, Omi Katsuse, Hirotake Uchikado, Yoshiko Furukawa, Hiroaki Hino, Kenji Kosaka, Piers C. Emson, Keiji Wada, Valina L. Dawson, Ted M. Dawson, Heii Arai, Eizo Iseki
Издательство: Oxford University Press
Источник: Journal of Neuropathology & Experimental Neurology
Ключевые слова: Parkinson's Disease Mechanisms and Treatments, Cellular transport and secretion, Lysosomal Storage Disorders Research
Другие ссылки: Journal of Neuropathology & Experimental Neurology (PDF)
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Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
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