Related Experiment Video
Updated: Aug 23, 2026

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
Neuronal apoptosis and protection: effects of nitric oxide and endoplasmic reticulum-related proteins
1Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. nomura@pharm.hokudai.ac.jp
Abstract:
This review presents recent findings with regard to the cellular and molecular mechanisms of neuronal apoptosis induced by cerebral ischemia/hypoxia. The protection of neuronal death by hypoxia-induced proteins in the endoplasmic reticulum (ER) is also reviewed. The excess amount of nitric oxide (NO) generated by inducible NO synthase (iNOS) up-regulated in response to ischemic stress causes neuronal apoptosis through following processes; 1) reduction in mitochondrial membrane potential, 2) release of cytochrome c from mitochondria, and 3) activation of caspase-9 and -3, although low concentrations of NO protect against neuronal death. In contrast, hypoxia induces expression of several proteins such as protein disulfide isomerase (PDI), ubiquilin and HRD1 in the endoplasmic reticulum (ER). PDI and ubiquilin are involved in the protection against neuronal apoptosis probably by interacting with each other and enhancing the effects of PDI as a molecular chaperon. HRD1 is also up-regulated by hypoxia in the ER and induces protection against hypoxia-induced neuronal apoptosis by activating the protein degradation system. The present review hopefully gives pertinent suggestions for further studies on the development of novel prophylactic/therapeutics for neuronal apoptosis-related diseases.
Related Concept Videos
Regulation of the Unfolded Protein Response
Cellular Injury V: Apoptosis and Autophagy
The Extrinsic Apoptotic Pathway
Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Export of Misfolded Proteins out of the ER
Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...

