Mitochondrial control of autophagic lysosomal pathway in Alzheimer's disease

When first described by Alois Alzheimer in 1907, AD was seen as a disorder that causes dementia and characterized by two defining neuropathological lesions, later associated with all forms of AD. While the etiology of AD remains largely unclear, there is accumulating evidence suggesting that mitochondrial dysfunction occurs prior to the onset of symptoms in AD. Mitochondria are exceptionally poised to play a crucial role in neuronal cell survival or death because they are regulators of both energy metabolism and apoptotic pathways. This review is mainly focused in the discussion of evidence suggesting a clear association between mitochondrial dysfunction, autophagy impairment and amyloid-beta accumulation in Alzheimer's disease pathophysiology. The knowledge that autophagic insufficiency may compromise the cellular degradation mechanisms that may culminate in the progressive accumulation of dysfunctional mitochondria, aberrant protein aggregates buildup and lysossomal burden shield new insights to the way we address Alzheimer's disease. In line with this knowledge an innovative window for new therapeutic strategies aimed to activate or ameliorate macroautophagy may be opened.