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Pathological Impact of Tau Proteolytical Process on Neuronal and Mitochondrial Function: a Crucial Role in Alzheimer's Disease - PubMed

Review

. 2023 Oct;60(10):5691-5707.

doi: 10.1007/s12035-023-03434-4. Epub 2023 Jun 19.

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Review

Pathological Impact of Tau Proteolytical Process on Neuronal and Mitochondrial Function: a Crucial Role in Alzheimer's Disease

Margrethe A Olesen et al. Mol Neurobiol. 2023 Oct.

Abstract

Tau protein plays a pivotal role in the central nervous system (CNS), participating in microtubule stability, axonal transport, and synaptic communication. Research interest has focused on studying the role of post-translational tau modifications in mitochondrial failure, oxidative damage, and synaptic impairment in Alzheimer's disease (AD). Soluble tau forms produced by its pathological cleaved induced by caspases could lead to neuronal injury contributing to oxidative damage and cognitive decline in AD. For example, the presence of tau cleaved by caspase-3 has been suggested as a relevant factor in AD and is considered a previous event before neurofibrillary tangles (NFTs) formation.Interestingly, we and others have shown that caspase-cleaved tau in N- or C- terminal sites induce mitochondrial bioenergetics defects, axonal transport impairment, neuronal injury, and cognitive decline in neuronal cells and murine models. All these abnormalities are considered relevant in the early neurodegenerative manifestations such as memory and cognitive failure reported in AD. Therefore, in this review, we will discuss for the first time the importance of truncated tau by caspases activation in the pathogenesis of AD and how its negative actions could impact neuronal function.

Keywords: Alzheimer’s disease; Caspase; Mitochondria; Neurodegeneration; Synaptic loss; Tau.

© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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