Synergistic enhancement of autophagy and lysosomal biogenesis by combined mTOR inhibition and TFEB activation

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Impaired autophagic flux in AD creates a 'traffic jam' with autophagosomes failing to fuse with lysosomes. Dual targeting of mTOR (to activate TFEB) and Patched1/TPC2 (to enhance lysosomal fusion) would synergistically increase clearance of Aβ42 and phosphorylated tau. However, the mechanistic chain involves too many targets (mTOR, TFEB, TPCN2), and the combination may introduce compounded toxicit