As autophagy involves degradation of protein complexes and organelles, and the aggregates occurring in PD and HD visible by light microscopy are not membrane bound and are larger than typical autophagosomes, it is likely that the monomeric and oligomeric species of the aggregate prone proteins are cleared by autophagy.16Autophagy is a major degradation pathway for various intracytosolic, aggregate prone, disease causing proteins associated with neurodegenerative disorders, such as mutant huntingtin (both N terminal fragments and full length forms) associated with HD, the A53T or A30P point mutants of causing familial PD, ataxin 3 involved in SCA3, mutant forms of superoxide dismutase 1 causing familial ALS and mutant forms of tau causing fronto temporal dementias.17, 18, 19, 20 Designer Fake Hermes, 21, 22Another lysosomal pathway that may clear certain aggregate prone proteins related to disease is chaperone mediated autophagy (CMA). This pathway involves recognition of a pentapeptide motif in client proteins by cytosolic heat shock cognate protein of 70 (hsc70), which mediates their ability to be taken up into lysosomes for degradation by the lysosome associated membrane protein type 2A (LAMP2A) that acts as a receptor. Thus Designer Fake Hermes, constitutive autophagy may play a pivotal role in the clearance of normally occurring misfolded proteins in the cells.
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