Oxidative stress: emerging mitochondrial and cellular themes and variations in neuronal injury.
Oxidative stress plays a central role in neuronal injury and cell death in acute and chronic pathological conditions. The cellular responses to oxidative stress embrace changes in mitochondria and other organelles, notably endoplasmic reticulum, and can lead to a number of cell death paradigms, which cover a spectrum from apoptosis to necrosis and include autophagy. In Alzheimer's disease, and other pathologies including Parkinson's disease, protein aggregation provides further cellular stresses that can initiate or feed into the pathways to cell death engendered by oxidative stress. Specific attention is paid here to mitochondrial dysfunction and programmed cell death, and the diverse modes of cell death mediated by mitochondria under oxidative stress. Novel insights into cellular responses to neuronal oxidative stress from a range of different stressors can be gained by detailed transcriptomics analyses. Such studies at the cellular level provide the key for understanding the molecular and cellular pathways whereby neurons respond to oxidative stress and undergo injury and death. These considerations underpin the development of detailed knowledge in more complex integrated systems, up to the intact human bearing the neuropathology, facilitating therapeutic advances.
Higgins
Gavin C
GC
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Beart
Philip M
PM
Shin
Yea Seul
YS
Chen
Minghui Jessica
MJ
Cheung
Nam Sang
NS
Nagley
Phillip
P
D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology; D028361:Mitochondrial Diseases / Q000150:complications / Q000473:pathology; D008954:Models, Biological; D009410:Nerve Degeneration / Q000473:pathology* / Q000503:physiopathology*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species