Oxidative Stress Events and Neuronal Dysfunction in Alzheimer’s Disease: Focus on APE1/Ref-1-Mediated Survival Strategies

摘要: Alzheimer’s disease (AD) is an important public health problem which affects millions of people worldwide. The major pathological hallmarks associated with AD are the accumulation amyloid beta (Aβ) in senile plaques and neurofibrillary tangles (NFT) made up hyperphosphorylated tau proteins. New findings suggest that oligomeric Aβ a more toxic species than fibrillar relevant to pathology. Although molecular mechanism(s) underlying not identified completely, various factors have been implicated development AD. Accumulating evidences point towards role oxidative stress mitochondrial dysfunction pathogenesis recognise them as early event development. Ageing considered greatest risk factor for linked causes somatic mutations DNA (mtDNA) over time leads genome instability dysfunction. Recent studies on patients transgenic mouse models precursor protein (APP) localise mitochondria, interact proteins, disrupt electron transport chain (ETC), increases reactive oxygen (ROS) level, impair axonal trafficking, thus leading synaptic damage cognitive decline It known whether cause or outcome declining function In order counteract maintain integrity, repair pathways exist, base excision (BER) pathway being predominant repairing oxidised lesions neuronal cells. APE1 central enzyme BER pathway, having both redox activities shown enhance survival after stress. Newer revealing maintenance function. this scenario, antioxidant-based therapy, could reduce modulate APE1, can serve effective treatment providing neuroprotection This book chapter summarises some recent developments understanding linking Aβ-induced stress, dysfunction, phytochemicals toward therapeutics.