The underlying mechanism of calcium toxicity-induced autophagic cell death and lysosomal degradation in early stage of cerebral ischemia

Anat Cell Biol. 2024 Apr 29. doi: 10.5115/acb.24.003. Online ahead of print.

Abstract

Cerebral ischemia is the important cause of worldwide disability and mortality, that is one of the obstruction of blood vessels supplying to the brain. In early stage, glutamate excitotoxicity and high level of intracellular calcium (Ca2+) are the major processes which can promote many downstream signaling involving in neuronal death and brain tissue damaging. Moreover, autophagy, the reusing of damaged cell organelles, is affected in early ischemia. Under ischemic conditions, autophagy plays an important role to maintain energy of the brain and its function. In the other hand, over intracellular Ca2+ accumulation triggers excessive autophagic process and lysosomal degradation leading to autophagic process impairment which finally induce neuronal death. This article reviews the association between intracellular Ca2+ and autophagic process in acute stage of ischemic stroke.

Keywords: Autophagy; Calcium toxicity; Cerebral ischemia; Lysosomal degradation; Neuronal cell death.