Abstract
Parkinson’s disease (PD) is a progressive movement disorder with multiple non-motor symptoms. Although family genetic mutations only account for a small proportion of the cases, these mutations have provided several lines of evidence for the pathogenesis of PD, such as mitochondrial dysfunction, protein misfolding and aggregation, and the impaired autophagy-lysosome system. Recently, vesicle trafficking defect has emerged as a potential pathogenesis underlying this disease. Rab GTPases, serving as the core regulators of cellular membrane dynamics, may play an important role in the molecular pathway of PD through the complex interplay with numerous factors and PD-related genes. This might shed new light on the potential therapeutic strategies. In this review, we emphasize the important role of Rab GTPases in vesicle trafficking and summarize the interactions between Rab GTPases and different PD-related genes.
Highlights
Parkinson’s disease (PD) is the second most prevalent chronic neurodegenerative disorder of aging, clinically characterized by motor symptoms including resting tremor, muscle rigidity, bradykinesia, postural instability and various non-motor symptoms (Shi et al, 2016)
The pathogenic mechanisms of different PD-related genes (SNCA, LRRK2, PTEN-induced kinase 1 (PINK1), Parkin and Transmembrane-protein 230 (TMEM230)) may share a converging molecular pathway, and Rab GTPases (Rabs) may serve as potential modulators in this pathway
Rab GTPases in Parkinson’s disease we summarize the physiological functions of Rabs and their interactions with multiple PD-related genes (Table 1)
Summary
Parkinson’s disease (PD) is the second most prevalent chronic neurodegenerative disorder of aging, clinically characterized by motor symptoms including resting tremor, muscle rigidity, bradykinesia, postural instability and various non-motor symptoms (Shi et al, 2016). The pathogenic mechanisms of different PD-related genes (SNCA, LRRK2, PINK1, Parkin and TMEM230) may share a converging molecular pathway, and Rabs may serve as potential modulators in this pathway. Rab9, whose effector is TIP47, facilitates the interaction between TIP47 and cytoplasmic terminal of mannose-6-phosphate receptors (M6PRs) during the formation of vesicles and maintains the recycle of M6PRs from the late endosome to the trans-Golgi network (TGN) (Aivazian et al, 2006).
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