LRRK2 in Parkinsons disease and dementia with Lewy bodiesReportar como inadecuado

LRRK2 in Parkinsons disease and dementia with Lewy bodies - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Molecular Neurodegeneration

, 1:17

First Online: 30 November 2006Received: 26 October 2006Accepted: 30 November 2006


BackgroundMutations in LRRK2 encoding leucine-rich repeat kinase 2 are thus far the most frequent genetic cause associated with autosomal dominant and idiopathic Parkinson-s disease PD. To examine whether LRRK2 is directly associated with neuropathology of PD and other related disorders, we analyzed LRRK2 in brains of patients affected by PD and dementia with Lewy bodies DLB using highly specific antibodies to LRRK2.

ResultsWe demonstrated that anti-LRRK2 antibodies strongly labelled brainstem and cortical Lewy bodies, the pathological hallmarks of PD and DLB, respectively. In addition, anti-LRRK2 also labelled brain vasculature, axons, and neuronal cell bodies. Interestingly, the immunocytochemical profile of LRRK2 varied with different antibodies depending upon specific antigenic sites along the LRRK2 protein. All anti-LRRK2 antibodies tested that were raised against various regions of LRRK2, were found to be immunoreactive to recombinant LRRK2 on Western blots. However, only the antibodies raised against the N-terminal and C-terminal regions of LRRK2, but not the regions containing folded protein domains, were positive in immunolabeling of Lewy bodies, suggesting a differential exposure of specific antigenic sites of LRRK2 on tissue sections.

ConclusionWe conclude that LRRK2 is a component of Lewy bodies in both PD and DLB, and therefore plays an important role in the Lewy body formation and disease pathogenesis. Information on the cellular localization of LRRK2 under normal and pathological conditions will deepen our understanding of its functions and molecular pathways relevant to the progression of PD and related disorders.

Electronic supplementary materialThe online version of this article doi:10.1186-1750-1326-1-17 contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Xiongwei Zhu - Asim Babar - Sandra L Siedlak - Qiwei Yang - Genta Ito - Takeshi Iwatsubo - Mark A Smith - George Perry -


Documentos relacionados