Ezetimibe, a NPC1L1 inhibitor, attenuates neuronal apoptosis through AMPK dependent autophagy activation after MCAO in rats

Experimental Neurology
Jing YuJohn H Zhang

Abstract

Autophagy activation exerts neuroprotective effects in the ischemic stroke model. Ezetimibe (Eze), a Niemann-Pick disease type C1-Like 1 (NPC1L1) pharmacological inhibitor, has been reported to protect hepatocytes from apoptosis via autophagy activation. In this study, we explored whether Eze could attenuate neuronal apoptosis in the rat model of middle cerebral artery occlusion (MCAO), specifically via activation of the AMPK/ULK1/autophagy pathway. Two hundred and one male Sprague-Dawley rats were subjected to transient MCAO followed by reperfusion. Eze was administered 1 h after MCAO. To elucidate the underlying molecular mechanism, Dorsomorphin, a selective AMPK inhibitor, and 3-methyladenine (3-MA), an autophagy inhibitor, were injected intracerebroventricularly before MCAO. Infarct volume, neurological score, brain cholesterol levels, immunofluorescence staining, Western blot, and Fluoro-Jade C (FJC) staining were used to evaluate the effects of Eze. The endogenous NPC1L1 expression increased and mainly expressed in neurons after MCAO. Intranasal administration of Eze reduced brain infarct volume at 24 and 72 h after MCAO, with improved short and long-term neurological functions after MCAO. Eze reduced brain cholesterol le...Continue Reading

Citations

Mar 11, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Zhenhua ZhouJohn H Zhang
Jan 31, 2020·Oxidative Medicine and Cellular Longevity·Jing YuJohn H Zhang
May 24, 2020·International Journal of Molecular Sciences·Fengming XuUta Dahmen
Mar 11, 2021·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Leonardo LorenteAlejandro Jiménez
Mar 11, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Meng WangYuchuan Ding
Apr 7, 2021·Pharmacology & Therapeutics·Amir AjoolabadyJun Ren
Jul 27, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Meng WangYuchuan Ding
Aug 3, 2021·Frontiers in Aging Neuroscience·Li LeiTao Li

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Acute Stroke

A stroke occurs when blood supply to the brain is interrupted depriving the brain of oxygen and nutrients. This feed focuses cerebrovascular accidents including ischemic and paralytic stroke.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.