Role of mitochondrial dysfunction, oxidative stress and autophagy in progression of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common form of dementia. The pathological hallmarks of AD are amyloid plaques [aggregates of amyloid beta (A)] and neurofibrillary tangles (aggregates of tau protein). Growing evidence suggests that tau accumulation is pathologically more relevant to the development of neurodegeneration and cognitive decline in AD patients than A plaques. Mitochondrial damage plays an important role in AD. Mitochondrial damage has been related to amyloid-beta or tau pathology or to the presence of specific presenilin-1 mutations. Elevate reactive oxygen species/reactive nitrogen species production and defective mitochondrial dynamic balance has been suggested to be the reason as well as the consequence of AD related pathology. Oxidative stress is a prominent early event in the pathogenesis of AD and is therefore believed to contribute to tau hyperphosphorylation. Several studies have shown that the autophagy pathway in neurons is important under physiological and pathological conditions. Therefore, this pathway plays a crucial role for the degradation of endogenous soluble tau. However, the relationship between mitochondrial dysfunctioning, oxidative stress, autophagy dysregulation, and neuronal cell death in AD remains unclear. Here, we review the latest progress in AD, with a special emphasis on mitochondrial dysfunctioning, oxidative stress, and autophagy. We also discuss the interlink mechanism of these three factors in AD.

Keywords: Alzheimer's disease; Amyloid beta (Aβ); Autophagy; Mitochondrial dysfunctioning; Neurofibrillary tangles (NFTs); Oxidative stress; Tauprotein.