Lysosomal Ca²⁺ release-facilitated TFEB nuclear translocation alleviates ischemic brain injury by attenuating autophagic/lysosomal dysfunction in neurons.

ABSTRACT: Neuronal death was frequently driven by autophagic/lysosomal dysfunction after ischemic stroke, whereas how to restore the impaired autophagic flux remained elusive. Autophagic/lysosomal signaling could be augmented after transcription factor EB (TFEB) nuclear translocation, which was facilitated by its dephosphorylation. A key TFEB dephosphorylase was calcineurin (CaN), whose activity was drastically regulated by cytosolic calcium ion concentration ([Ca²⁺]) controlled by lysosomal Ca²⁺ channel-like protein of TRPML1. Our research shows that ML-SA1, an agonist of the TRPML1 channel, significantly enhanced the lysosomal Ca²⁺ release and the CaN expression in penumbric neurons, subsequently promoted TFEB nuclear translocation, and greatly reversed autophagy/l

SUBMITTER: Lei Q 

PROVIDER: S-EPMC11496619 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature