Aldehyde dehydrogenase 2 in the spotlight: The link between mitochondria and neurodegeneration

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HighlightsNeurodegenerative diseases are threatening conditions that affect life-quality and life-span of the affected patients.ALDH2 is a critical enzyme involved in neurotoxic mechanisms of PD and AD.4-HNE is considered a fundamental signaling molecules in the pathogenesis of AD and its detoxification depends on ALDH2.ALDH2 activation is proposed as a therapeutic approach for PD since the enzyme plays a crucial role in mitochondrial normal function maintenance.Growing body of evidence suggests that mitochondrial dysfunctions and resultant oxidative stress are likely responsible for many neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Aldehyde dehydrogenase (ALDH) superfamily plays a crucial role in several biological processes including development and detoxification pathways in the organism. In particular, ALDH2 is crucial in the oxidative metabolism of toxic aldehydes in the brain, such as catecholaminergic metabolites (DOPAL and DOPEGAL) and the principal product of lipid peroxidation process 4-HNE. This review aims to deepen the current knowledge regarding to ALDH2 function and its relation with brain-damaging processes that increase the risk to develop neurodegenerative disorders. We focused on relevant literature of what is currently known at molecular and cellular levels in experimental models of these pathologies. The understanding of ALDH2 contributions could be a potential target in new therapeutic approaches for PD and AD due to its crucial role in mitochondrial normal function maintenance that protects against neurotoxicity.

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