02440nas a2200229   4500008004100000022001400041245007500055210006900130260000800199520163100207653002401838653003301862653004501895653001901940653002801959653000801987653002001995653003202015100002802047700003602075856009902111       2020                        eng d  a0272-434000aAutophagic pathways to clear the tau aggregates in alzheimer's disease0 aAutophagic pathways to clear the tau aggregates in alzheimers di  cJUN3 a<p>Tau is a microtubule-associated protein with an intrinsically unstructured conformation. Tau is subjected to several pathological post-translational modifications (PTMs), leading to its loss of interaction with microtubules and accumulation as neurofibrillary tangles (NFTs) in neurons. Tau aggregates impede functions of endoplasmic reticulum and mitochondria leading to the generation of oxidative stress and in turn amplifying the Tau aggregation. Tau is channelled to chaperones for folding into their native form, which otherwise causes its degradation and clearance. Cellular response triggers the activation of ubiquitin-proteasome system or autophagy to facilitate Tau degradation, based on the PTMs or mutations associated with Tau. Further, autophagy can be selective where Hsc70 interacts with Tau in monomeric, oligomeric and aggregated form and drives its clearance by chaperone-mediated autophagy pathway (CMA). Lysosome-associated membrane proteins-2A (LAMP-2A) is the key player of CMA that recognises Hsc70-Tau complex and triggers the downstream cascade. Thus, it becomes challenging for mutant Tau to be cleared by CMA as it loses its affinity for Hsc70 and LAMP-2A. In such a scenario, Tau might be degraded by macroautophagy otherwise sequestered by aggresomes. Henceforth, the degradation of Tau and its blockage that is associated with various PTMs of Tau would explain the dynamics of Tau degradation or accumulation in AD. Further, unveiling the role of accessory proteins involved in these degradation pathways would help in understanding their loss of function and preventing Tau clearance.</p>
10aAlzheimer's disease10aChaperone-mediated autophagy10aLysosome-associated membrane proteins-2A10aMacroautophagy10aNeurofibrillary tangles10aTau10aTau degradation10aUbiquitin-proteasome system1 aGorantla, Nalini, Vijay1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/autophagic-pathways-clear-tau-aggregates-alzheimers-disease