Endoplasmic reticulum stress in brain damage.
The efficient functioning of the ER is indispensable for most of the cellular activities and survival. Disturbances in the physiological functions of the ER result in the activation of a complex set of signaling pathways from the ER to the cytosol and nucleus, and these are collectively known as unfolded protein response (UPR), which is aimed to compensate damage and can eventually trigger cell death if ER stress is severe or persists for a longer period. The precise molecular mechanisms that facilitate this switch in brain damage have yet to be understood completely with multiple potential participants involved. The ER stress-associated cell death pathways have been recognized in the numerous pathophysiological conditions, such as diabetes, hypoxia, ischemia/reperfusion injury, and neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and bipolar disorder. Hence, there is an emerging need to study the basic molecular mechanisms of ER stress-mediating multiple cell survival/death signaling pathways. These molecules that regulate the ER stress response would be potential drug targets in brain diseases.
Division of Pharmacology, Central Drug Research Institute, (CSIR), Chatter Manzil Palace, Lucknow, India.
Ram
R
Raghubir
Venkata Prasuja
VP
Nakka
Suresh L
SL
Mehta
D051702:Activating Transcription Factor 6 / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001927:Brain Diseases / Q000503:physiopathology*; D020169:Caspases / Q000502:physiology; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological / Q000502:physiology*; D051742:Transcription Factor CHOP / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D056811:Unfolded Protein Response; D019892:eIF-2 Kinase / Q000502:physiology
D051702:Activating Transcription Factor 6; D020169:Caspases; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D000071701:Regulatory Factor X Transcription Factors; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D019892:eIF-2 Kinase; C497111:ATF6 protein, human; C486556:Ern2 protein, mouse