11 November 2022>: Review Articles
Autophagy and Its Association with Genetic Mutations in Parkinson Disease
Nour S. Erekat EF*DOI: 10.12659/MSM.938519
Med Sci Monit 2022; 28:e938519
Figure 1 Association between α-synuclein and autophagy in Parkinson disease. (A) Overexpression of wild-type α-synuclein impairs autophagy by preventing Ras-associated binding 1A (RAB1A) protein, leading to the mislocalization of the early autophagy protein ATG9. (B) Overexpression of wild-type or mutant α-synuclein was shown to block autophagy by binding to both cytosolic and nuclear high mobility group box 1 (HMGB1), compromising the cytosolic translocation of HMGB1, inhibiting HMGB1-Beclin 1 (BECN1) binding, and enhancing BECN1- B-cell lymphoma 2 (BCL2) binding. (C) Mutant α-synuclein inhibits chaperone-mediated autophagy (CMA) by acting as uptake blockers blocking lysosome-associated membrane protein 2A (LAMP2A)-channel for the translocation of proteins into lysosomes. Subsequently, mutant α-synuclein accumulates, leading to the compensatory activation of macroautophagy. This figure was generated using Microsoft PowerPoint Software, version 10, Microsoft Corp., USA.