title: Common mechanisms of Alzheimer's disease and ischemic stroke: the role of protein kinase C in the progression of age-related neurodegeneration.
abstract: Ischemic stroke and Alzheimer's disease (AD), despite being distinct disease entities, share numerous pathophysiological mechanisms such as those mediated by inflammation, immune exhaustion, and neurovascular unit compromise. An important shared mechanistic link is acute and chronic changes in protein kinase C (PKC) activity. PKC isoforms have widespread functions important for memory, blood-brain barrier maintenance, and injury repair that change as the body ages. Disease states accelerate PKC functional modifications. Mutated forms of PKC can contribute to neurodegeneration and cognitive decline. In some cases the PKC isoforms are still functional but are not successfully translocated to appropriate locations within the cell. The deficits in proper PKC translocation worsen stroke outcome and amyloid-β toxicity. Cross talk between the innate immune system and PKC pathways contribute to the vascular status within the aging brain. Unfortunately, comorbidities such as diabetes, obesity, and hypertension disrupt normal communication between the two systems. The focus of this review is to highlight what is known about PKC function, how isoforms of PKC change with age, and what additional alterations are consequences of stroke and AD. The goal is to highlight future therapeutic targets that can be applied to both the treatment and prevention of neurologic disease. Although the pathology of ischemic stroke and AD are different, the similarity in PKC responses warrants further investigation, especially as PKC-dependent events may serve as an important connection linking age-related brain injury.
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV, USA The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA.
authors.forename: Brandon P
authors.initials: BP
authors.lastname: Lucke-Wold
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV, USA The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Turner
authors.affiliation: The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV, USA.
authors.forename: Aric F
authors.initials: AF
authors.lastname: Logsdon
authors.affiliation: The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Simpkins
authors.affiliation: Blanchette Rockefeller Neurosciences Institute, Morgantown, WV, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Alkon
authors.affiliation: The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Smith
authors.affiliation: The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV, USA The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Tan
authors.affiliation: The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Huber
authors.affiliation: Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV, USA The Center for Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Rosen
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
chemical_list: D011493:Protein Kinase C
keywords: Alzheimer's disease; blood-brain barrier; immune exhaustion; innate immunity; ischemic stroke; protein kinase C
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