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dc.contributor.authorYu, Qing
dc.contributor.authorDu, Fang
dc.contributor.authorDouglas, Justin T.
dc.contributor.authorYu, Haiyang
dc.contributor.authorYan, Shirley ShiDu
dc.contributor.authorYan, Shi Fang
dc.identifier.citationYu, Q., Du, F., Douglas, J. T., Yu, H., Yan, S. S., & Yan, S. F. (2017). Mitochondrial Dysfunction Triggers Synaptic Deficits via Activation of p38 MAP Kinase Signaling in Differentiated Alzheimer’s Disease Trans-Mitochondrial Cybrid Cells. Journal of Alzheimer’s Disease : JAD, 59(1), 223–239.
dc.description.abstractLoss of synapse and synaptic dysfunction contribute importantly to cognitive impairment in Alzheimer’s disease (AD). Mitochondrial dysfunction and oxidative stress are early pathological features in AD-affected brain. However, the effect of AD mitochondria on synaptogenesis remains to be determined. Using human transmitochondrial “cybrid” (cytoplasmic hybrid) neuronal cells whose mitochondria were transferred from platelets of patients with sporadic AD or age-matched non-AD subjects with relatively normal cognition, we provide the first evidence of mitochondrial dysfunction compromises synaptic development and formation of synapse in AD cybrid cells in response to chemical-induced neuronal differentiation. Compared to non-AD control cybrids, AD cybrid cells showed synaptic loss which was evidenced by a significant reduction in expression of two synaptic marker proteins: synaptophysin (presynaptic marker) and postsynaptic density protein-95, and neuronal proteins (MAP-2 and NeuN) upon neuronal differentiation. In parallel, AD-mediated synaptic deficits correlate to mitochondrial dysfunction and oxidative stress as well as activation of p38 MAP kinase. Notably, inhibition of p38 MAP kinase by pharmacological specific p38 inhibitor significantly increased synaptic density, improved mitochondrial function, and reduced oxidative stress. These results suggest that activation of p38 MAP kinase signaling pathway contributes to AD-mediated impairment in neurogenesis, possibly by inhibiting the neuronal differentiation. Our results provide new insight into the crosstalk of dysfunctional AD mitochondria to synaptic formation and maturation via activation of p38 MAP kinase. Therefore, blockade of p38 MAP kinase signal transduction could be a potential therapeutic strategy for AD by alleviating loss of synapses.en_US
dc.publisherIOS Pressen_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectCybrid cellsen_US
dc.subjectMitochondrial dysfunctionen_US
dc.subjectSynaptic Deficitsen_US
dc.titleMitochondrial Dysfunction Triggers Synaptic Deficits via Activation of p38 MAP Kinase Signaling in Differentiated Alzheimer’s Disease Trans-Mitochondrial Cybrid Cellsen_US
kusw.kudepartmentHiguchi Biosciences Centeren_US
kusw.oanotesPer SHERPA/RoMEO 6/7/2018: Author's Pre-print: green tick author can archive pre-print (ie pre-refereeing) Author's Post-print: green tick author can archive post-print (ie final draft post-refereeing) Publisher's Version/PDF: cross author cannot archive publisher's version/PDF General Conditions:

On author's personal website, institutional website or funder's website, including PubMed Central Non-commercial use only Publisher copyright and source must be acknowledged Author's version can be used Publisher's version/PDF cannot be used
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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