MITOPHAGY AND SPORADIC ALZHEIMER'S DISEASE

Mitochondria are essential organelles for cells energetic processes. Mitophagy is responsible for the basal mitochondrial turnover that eliminates mitochondria. This process belongs to autophagy which is a catabolic mechanism and is needful for intracellular homeostasis. Mitochondrial impairment is repeatedly documented in Alzheimer's disease (AD) as well as in post-mortem brain tissue. AD is a chronic neurodegenerative disease with characteristic histopathology abnormalities: amyloid-beta plaques and neurofibrillary tangles of hyperfosforylated tau protein. For late-onset AD (sporadic form) "mitochondrial cascade hypothesis" was proposed, which suppose that mitochondrial dysfunction represents primary pathology in this disease. The relationship between AD and mitophagy impairment is not clear. Results in animal models suggest that mitophagy is related to disease-defining pathology, however affiliation on these processes is not known. In AD patients was shown that mitophagy is changed in gene level and for the next level in whole mitochondria. Further field of study is focused on mitochondrial DNA which is relatively unstable and with aging there is a progress in mutation. We are interested in relationship between mitophagy and sporadic AD and also relationship between mitophagy and typical AD pathology. Animal models currently used did not fully represent sporadic form of AD, which limits the applicability of research results to study human late-onset AD. The question is, if pharmacological agents and lifestyle interventions which enhance mitophagy and improve "mitochondrial health" will be the new way of AD treatment.