Malfunctioning of CMA plays a key role in an increasing number of severe human disorders. 8 Furthermore, because of its selectivity, CMA can play a regulatory role in processes like proteostasis, cellular energetics, and immune system activity by helping to modulate intracellular levels of enzymes, transcription factors, and cell maintenance proteins. This permits specific proteins to be removed without interfering with surrounding proteins, making CMA an effective method for the breakdown of damaged or aberrant proteins and surplus subunits of multi-protein complexes. 7 Individual proteins that are degraded by this autophagic pathway are chosen based on a recognition KFERQ-like consensus motif. 6 It is distinguished by its selectivity and the fact that, unlike the other two lysosomal pathways, it does not require vesicle formation substrate proteins appear to pass the lysosomal membrane directly to enter the lysosomal lumen. 4, 5Ĭhaperone-mediated autophagy (CMA) is a type of autophagy that is specialized in protein degradation and is based on the individual translocation of a cargo protein across the lysosomal membrane. 3 Autophagy is classified into three types: macroautophagy (MA), microautophagy (MA), and chaperone-mediated autophagy (CMA). 2Īutophagy is a highly conserved mechanism for delivering cytoplasmic components for lysosomal degradation in order to maintain the homeostatic balance of cellular protein and organelle synthesis, degradation, and recycling. 1 The ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP) are important systems found in almost all cell types that mediate the degradation of intracellular proteins into their constitutive amino acids. It is based on a delicate balance of protein synthesis and breakdown. Therefore, in this paper we introduce the basic processes, regulatory mechanisms, and physiological functions of CMA evidences supporting the role of impaired CMA function in neurodegeneration and cancer and the potential of how targeting CMA could be a promising therapeutic method for the two diseases.Ĭellular protein homeostasis, also referred to as proteostasis, is essential for cellular function and survival. Manipulation of CMA activity may be effective therapeutic strategies for treating these diseases. The presence of changes in CMA in these diseases disorders raises the idea of targeting CMA to restore cellular homeostasis as a potential therapeutic method. Once a tumor has grown, it also helps tumor survival and the metastatic cascade. CMA has been shown to act as a tumor suppressor in cancer by destroying specific tumor promoters. ![]() In various neurodegenerative disorders, especially in their later stages, CMA activity declines. Neurodegenerative diseases and cancer have received the most attention. This pathway’s dysfunction has been linked to several diseases and disorders. CMA helps to maintain cellular homeostasis by regulating protein quality, bioenergetics, and substrate-associated cellular processes at the right moment. Among the three forms of autophagy, chaperone-mediated autophagy (CMA) is distinct from macroautophagy and microautophagy it does not require the formation of vacuoles and only degrades selected individual proteins. Autophagy is a cellular process that degrades and recycles damaged or long-lived proteins, misfolded proteins, and damaged or abnormal organelles in order to preserve homeostasis. Proteostasis, also known as protein homeostasis, is critical for cell survival.
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