Role of Protein Conformational Dynamics and DNA Integrity in Relevance to Neuronal Cell Death in Neurodegeneration

Veer      Bala Gupta; Muralidhar   L.   Hegde; K.   S.   Jagnnathan Rao

Abstract

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 Alzheimers disease (AD) and other neurodegenerative disorders is not understood till now. Amyloid beta (Aβ) proteins are the hallmark toxic proteins known to cause the activation of apoptotic cascades via caspase dependent and caspase-independent pathways. Aβ 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.

Keywords: Amyloid, Alzheimer's disease, apoptosis, mitochondria, endoplasmic reticulum, DNA damage, protein conformation, DNA binding