Oxidative Genome Damage and Its Repair in Neurodegenerative Diseases: Function of Transition Metals as a Double-Edged Sword

摘要: The neurons in the central nervous system (CNS) with high O2 consumption and prolonged life span are chronically exposed to levels of reactive oxygen species (ROS). Accumulation ROS-induced genome damage form oxidized bases single-strand breaks (SSBs) as well their defective or reduced repair brain has been implicated etiology various neurological disorders including Alzheimer's/Parkinson's diseases (AD/PD). Although inactivating mutations some DNA genes have linked hereditary neurodegenerative diseases, underlying mechanisms deficiencies for sporadic is not understood. predominantly repaired via highly conserved regulated base excision/SSB (BER/SSBR) pathway. We recently made an interesting discovery that transition metals iron copper, which accumulate excessively brains AD, PD, other act a 'double-edged sword' by inducing genotoxic ROS inhibiting at same time. These inhibit excision activity NEIL family glycosylases oxidizing them, changing structure, binding downstream proteins. Metal chelators reducing agents partially reverse inhibition, while curcumin both chelating activities reverses inhibition nearly completely. In this review, we discussed possible etiological linkage BER/SSBR defects therapeutic potential metal restoring capacity.