Role of protein conformational dynamics and DNA integrity in relevance to neuronal cell death in neurodegeneration.
Apoptosis has been implicated in the pathogenesis of various neurodegenerative disorders, although the extent to which it is responsible for the neurodegeneration along with other kind of cell death events is not known. Eventhough much information is available today on the apoptotic cascades in general, the precise mechanism and the exact sequence of events leading to neuronal degeneration in Alzheimer's disease (AD) and other neurodegenerative disorders is not understood till now. Amyloid beta (Abeta) proteins are the hallmark toxic proteins known to cause the activation of apoptotic cascades via caspase dependent and caspase-independent pathways. Abeta can cause neuronal apoptosis through multiple mechanisms involving mitochondria and endoplasmic reticulum as the key organelles. In this review, we have discussed the role of apoptosis in neurodegeneration and provided new thoughts on the role of protein conformational dynamics and DNA integrity associated with neurodegenerative disorders. An insight on whether the apoptosis observed in the neurodegenerative disorders is of any functional advantage has been discussed.
Gupta
Veer Bala
VB
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore-570020, India.
Hegde
Muralidhar L
ML
Rao
K S Jagnnathan
KS
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011487:Protein Conformation; D015398:Signal Transduction / Q000235:genetics
D016229:Amyloid beta-Peptides; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins