LRRK2 as a Potential Genetic Modifier of Synucleinopathies: Interlacing the Two Major Genetic Factors of Parkinson's Disease.
Parkinson's disease (PD) and related Lewy body diseases are characterized by deposition of α-synuclein aggregates in both the central nervous system and peripheral nervous system. Synucleinopathy lesions spread to larger brain areas as the disease progresses, and prion-like cell-to-cell transmission of aggregated α-synuclein is thought to be the underlying mechanism for this pathological spreading. LRRK2 is another protein linked to the pathogenesis of PD, and its presence in Lewy bodies has attracted much attention as to whether LRRK2 and α-synuclein interplay during the pathogenesis of PD. However, the relationship between these two crucial proteins still remains unclear. In this review article, we will discuss the current state of knowledge in terms of how these proteins cause the disease and provide the hypothetical mechanisms by which LRRK2 might modify the generation and progression of synucleinopathy.
Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul 143-701, Korea.
Cheol Hwan
CH
Hyun
Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul 143-701, Korea.
Chae Young
CY
Yoon
Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul 143-701, Korea. ; Department of Anatomy, School of Medicine, Konkuk University, Seoul 143-701, Korea.
He-Jin
HJ
Lee
Department of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul 143-701, Korea. ; Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul 143-701, Korea.
Seung-Jae
SJ
Lee
LRRK2; Parkinson's disease; alpha-synuclein; neurodegeneration; synucleinopathy; transmission