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Caspase-Cleaved Tau Impairs Mitochondrial Dynamics in Alzheimer’s Disease

dc.contributor.authorPérez M.J.
dc.contributor.authorVergara-Pulgar K.
dc.contributor.authorJara C.
dc.contributor.authorCabezas-Opazo F.
dc.contributor.authorQuintanilla R.A.
dc.date.accessioned2020-09-02T22:26:23Z
dc.date.available2020-09-02T22:26:23Z
dc.date.issued2018
dc.identifier10.1007/s12035-017-0385-x
dc.identifier.citation55, 2, 1004-1018
dc.identifier.issn08937648
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5893
dc.descriptionAlzheimer’s disease (AD) is characterized by the presence of aggregates of tau protein. Tau truncated by caspase-3 (D421) or tau hyperphosphorylated at Ser396/S404 might play a role in the pathogenesis of AD. Mitochondria are dynamic organelles that modify their size and function through mitochondrial dynamics. Recent studies have shown that alterations of mitochondrial dynamics affect synaptic communication. Therefore, we studied the effects of pathological forms of tau on the regulation of mitochondrial dynamics. We used primary cortical neurons from tau(−/−) knockout mice and immortalized cortical neurons (CN1.4) that were transfected with plasmids containing green fluorescent protein (GFP) or GFP with different tau forms: full-length (GFP-T4), truncated (GFP-T4C3), pseudophosphorylated (GFP-T42EC), or both truncated and pseudophosphorylated modifications of tau (GFP-T4C3-2EC). Cells expressing truncated tau showed fragmented mitochondria compared to cells that expressed full-length tau. These findings were corroborated using primary neurons from tau(−/−) knockout mice that expressed the truncated and both truncated and pseudophosphorylated forms of tau. Interestingly, mitochondrial fragmentation was accompanied by a significant reduction in levels of optic atrophy protein 1 (Opa1) in cells expressing the truncated form of tau. In addition, treatment with low concentrations of amyloid-beta (Aβ) significantly reduced mitochondrial membrane potential, cell viability, and mitochondrial length in cortical cells and primary neurons from tau(−/−) mice that express truncated tau. These results indicate that the presence of tau pathology impairs mitochondrial dynamics by reducing Opa1 levels, an event that could lead to mitochondrial impairment observed in AD. © 2017, Springer Science+Business Media New York.
dc.language.isoen
dc.publisherHumana Press Inc.
dc.subjectAlzheimer’s disease
dc.subjectMitochondria
dc.subjectNeurodegeneration
dc.subjectOpa1
dc.subjectTau
dc.subjectamyloid beta protein
dc.subjectcaspase
dc.subjectgreen fluorescent protein
dc.subjectmitochondrial protein
dc.subjectoptic atrophy protein 1
dc.subjecttau protein
dc.subjectunclassified drug
dc.subjecttau protein
dc.subjectAlzheimer disease
dc.subjectanimal cell
dc.subjectArticle
dc.subjectbrain cell
dc.subjectcell size
dc.subjectcell viability
dc.subjectcontrolled study
dc.subjectdisorders of mitochondrial functions
dc.subjectdown regulation
dc.subjectimmortalized cell line
dc.subjectmitochondrial membrane potential
dc.subjectmouse
dc.subjectnonhuman
dc.subjectprotein cleavage
dc.subjectprotein expression
dc.subjectprotein modification
dc.subjectprotein phosphorylation
dc.subjectAlzheimer disease
dc.subjectanimal
dc.subjectbrain
dc.subjectgenetics
dc.subjectknockout mouse
dc.subjectmetabolism
dc.subjectmitochondrial dynamics
dc.subjectmitochondrion
dc.subjectnerve cell
dc.subjectphosphorylation
dc.subjectphysiology
dc.subjectAlzheimer Disease
dc.subjectAnimals
dc.subjectBrain
dc.subjectGreen Fluorescent Proteins
dc.subjectMembrane Potential, Mitochondrial
dc.subjectMice
dc.subjectMice, Knockout
dc.subjectMitochondria
dc.subjectMitochondrial Dynamics
dc.subjectNeurons
dc.subjectPhosphorylation
dc.subjecttau Proteins
dc.titleCaspase-Cleaved Tau Impairs Mitochondrial Dynamics in Alzheimer’s Disease
dc.typeArticle


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