![]() ![]() ![]() The efficiency of the CMA pathway can be affected by the velocity of assembly and disassembly of the LAMP2A translocation complex. After the substrate translocates into the lysosome lumen, the LAMP2A multimer disassembles into monomers and returns to the cytosol for reuse. The binding between substrate and LAMP2A promotes LAMP2A multimerization to form a translocation complex during CMA. LAMP2A contains a cytosolic tail different from the other variants of the LAMP2 genes. Moreover, the large number of defective proteins overwhelm CMA and eventually paralyze it. The common feature of AD and other NDs is the presence of toxic protein aggregates in the patient’s brain. With increasing age, the efficiency of CMA is lowered, which increases the risk of harmful proteins accumulating into insoluble clumps that damage cells. In CMA, heat shock cognate 71 kDa protein (HSC70) chaperones bind to damaged or defective proteins containing KFERQ-like sequences and transport them to the lysosomes via lysosome-associated membrane protein 2A (LAMP2A). In microautophagy, the lysosomes directly uptake the cytosolic compounds through membrane enwrapping. During macroautophagy, the cargo is sequestrated by double-membrane vesicles-autophagosomes and transported to the lysosome. Macroautophagy is the best-studied type of autophagy. Autophagy is classified as macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA) based on how cargo is delivered to the lysosome. ![]()
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