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. 2022 Apr 15;11(8):1353. doi: 10.3390/cells11081353

Figure 1.

Figure 1

Disrupted protein clearance systems (autophagy-lysosome pathway and ubiquitin-proteasome pathway) in PD motor neurons and GCase dysfunction. (a) Macroautophagy. (b) Chaperone mediated autophagy (CMA) is a more selective process and targets KFERQ amino-acid-motif containing proteins such as αSyn. (c) Microautophagy or pinocytosis of intracellular contents. (d) Defective ubiquitin-proteasome system (UPS) failure in eliminating misfolded proteins tagged with ubiquitin such as GCase precede aggresome formation and neurodegeneration. Defects in GCase turnover [46] lead to glucosylceramide (GlcCer) accumulation, which later contributes to αSyn aggregation and impaired autophagy [25]. Altogether, impaired protein-clearance systems cause neurodegeneration in PD (created with BioRender.com. accessed on 1 January 2022). Events leading to GCase dysfunction and its consequences are indicated by red-color arrows. Dashed arrows represent a series of reactions, and dashed arrows with the question mark in the middle indicate unknown mechanisms.