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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The Influence of Trehalose on Atherosclerosis and Hepatic Steatosis in Apolipoprotein E Knockout Mice

Aneta Stachowicz, Anna Wiśniewska, Katarzyna Kuś, Anna Kiepura, Anna Gębska, Mariusz Gajda, Magdalena Białas, Justyna Totoń-Żurańska, Kamila Stachyra, Maciej Suski, Jacek Jawień, Ryszard Korbut and Rafał Olszanecki

Atherosclerosis and nonalcoholic fatty liver disease (NAFLD) are frequent causes of death in the Western countries. Recently, it has been shown that autophagy dysfunction plays an important role in the pathogenesis of both atherosclerosis and NAFLD; thus, activators of autophagy might be useful for novel therapeutic interventions. Trehalose—a naturally occuring disaccharide present in plants, bacteria, fungi, insects, and certain types of shrimps—is a known inducer of autophagy. However, …

Int. J. Mol. Sci. 2019;20:1552.
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Microglial autophagy–associated phagocytosis is essential for recovery from neuroinflammation

Rasmus Berglund, Andre Ortlieb Guerreiro-Cacais, Milena Z. Adzemovic, Manuel Zeitelhofer, Harald Lund, Ewoud Ewing, Sabrina Ruhrmann, Erik Nutma, Roham Parsa, Melanie Thessen-Hedreul, Sandra Amor, Robert A. Harris, Tomas Olsson and Maja Jagodic

Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration in the central nervous system (CNS). The capacity of microglia to clear tissue debris is essential for maintaining and restoring CNS homeostasis. This capacity diminishes with age, and age strongly associates with MS disease progression, although the underlying mechanisms are still largely elusive. Here, we demonstrate that the recovery …

Sci. Immunol. 2020;5:eabb5077.
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