TFEB

Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis

Ismail Sergin, Trent D. Evans, Xiangyu Zhang, Somashubhra Bhattacharya, Carl J. Stokes, Eric Song, Sahl Ali, Babak Dehestani, Karyn B. Holloway, Paul S. Micevych, Ali Javaheri, Jan R. Crowley, Andrea Ballabio, Joel D. Schilling, Slava Epelman, Conrad C. Weihl, Abhinav Diwan, Daping Fan, Mohamed A. Zayed & Babak Razani

Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy–lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator …

Nat. Commun. 2017;8:15750.
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