Elucidating the pathophysiological role of the apoptosis inducing factor 1 (AIF1) in Alzheimer's disease: a review of its participation in other pathologies

Solé Ariza, Aina

Elucidating the pathophysiological role of the apoptosis inducing factor 1 (AIF1) in Alzheimer's disease: a review of its participation in other pathologies

Citation

Solé Ariza, A. Elucidating the pathophysiological role of the apoptosis inducing factor 1 (AIF1) in Alzheimer's disease: a review of its participation in other pathologies. 2021. handle: http://hdl.handle.net/10230/48458

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Abstract

Alzheimer’s disease (AD) is the most common cause of age-related dementia, whose progression and development are explained by two well-based hypotheses. The amyloid cascade hypothesis proposes the aggregation of the amyloid ß-peptide (Aß) as the key event that triggers AD, whereas the mitochondrial cascade hypothesis claims that neurodegeneration is caused by oxidative stress and mitochondrial dysfunction. Even so, both hypotheses are not independent since a relationship between them is already known. Many questions about its physiopathology, however, remain unanswered. The present review proposes the possible participation of the apoptosis inducing factor 1 (AIF1) in AD, a highly relevant mitochondrial protein both for cell survival (OXPHOS process) and for cell death (caspase-independent apoptosis). According to the known functions the AIF1 performs in other pathologies, it can be suggested that the Aß accumulation and oxidative stress produces the release of pro-apoptotic AIF1, which contributes to mitochondrial dysfunction and apoptosis in hippocampus neurons. Nevertheless, the dual functionality of AIF1 represents one of the greatest challenges to clearly define the involvement of the protein in AD, so further studies are required in this direction.