Extrinsic and intrinsic pathways of apoptosis and related molecules in ischemic stroke

Document Type : Narrative Review

Authors

1 Oral and Maxillofacial Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Oral and Maxillofacial Pathology, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran

10.22034/CAJMPSI.2021.04.04

Abstract

Cerebral ischemia is a disease in which there is not enough blood flow to the brain tissue for metabolism. Stroke includes two types of ischemic with a frequency of approximately 85% and hemorrhagic with a frequency of approximately 15%. Various mechanisms cause neuronal death in cerebral ischemia, including increased extracellular glutamate amino acid concentration, inflammation, oxidative stress, apoptosis, and necrosis-induced cell death. Each of these mechanisms appears to extend through distinct molecular cascades. Although several mechanisms are involved in the pathogenesis of cerebral ischemia, apoptosis plays a major role in cell death after cerebral ischemia. Some minutes after the onset of focal cerebral ischemia, the core region in the brain ischemic tissues severe blood flow is fatally damaged, leading to cell death. Following cerebral ischemia, apoptosis begins through two general pathways. One is the intrinsic pathway that occurs mainly in the mitochondria and releases cytochrome C and is involved in the stimulation of caspase-3. The other is the extrinsic pathway that begins with the activity of death receptors on the surface of neurons and leads to the stimulation of caspase-8. Key molecules are involved in the process of cell apoptosis, the most important of which are calpain, caspases, and c-Jun N-terminal kinases. This study aimed to describe the process of apoptosis in cerebral ischemia and to introduce the above-mentioned molecules.

Graphical Abstract

Extrinsic and intrinsic pathways of apoptosis and related molecules in ischemic stroke

Highlights

  • Cerebral ischemia is a disease in which there is not enough blood flow to the brain tissue for metabolism.
  • Apoptosis plays a major role in cell death after cerebral ischemia.
  • Following cerebral ischemia, apoptosis begins through two general pathways, intrinsic and extrinsic.
  • Calpain, caspases, and JNK are among the most important molecules involved in cerebral ischemia-induced apoptosis.

Keywords

Main Subjects


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