title: Activation of neuronal extracellular receptor kinase (ERK) in Alzheimer disease links oxidative stress to abnormal phosphorylation.
abstract: Responses to increased oxidative stress may be the common mechanism responsible for the varied cytopathology of Alzheimer disease (AD). A possible link in support of this hypothesis is that one of the most striking features of AD, the abnormal accumulation of highly phosphorylated tau and neurofilament proteins, may be brought about by extracellular receptor kinase (ERK) whose activation is a common response to oxidative stress. In this study, we demonstrate that activated ERK is specifically increased in the same vulnerable neurons in AD that are the site of oxidative damage and abnormal phosphorylation. These findings suggest that ERK dysregulation, likley resulting from oxidative stress, could play an important role in the increased phosphorylation of cytoskeletal proteins observed in AD.
authors.affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: G
authors.initials: G
authors.lastname: Perry
authors.forename: H
authors.initials: H
authors.lastname: Roder
authors.forename: A
authors.initials: A
authors.lastname: Nunomura
authors.forename: A
authors.initials: A
authors.lastname: Takeda
authors.forename: A L
authors.initials: AL
authors.lastname: Friedlich
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: A K
authors.initials: AK
authors.lastname: Raina
authors.forename: N
authors.initials: N
authors.lastname: Holbrook
authors.forename: S L
authors.initials: SL
authors.lastname: Siedlak
authors.forename: P L
authors.initials: PL
authors.lastname: Harris
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016875:tau Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases