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CRMP2 hyperphosphorylation is characteristic of Alzheimer's disease and not a feature common to other neurodegenerative diseases.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Williamson, Ritchie Aalten, Lidy Van Mann, David M. A. Platt, Bettina Plattner, Florian Bedford, Lynn Mayer, James W. Howlett, David Scott Usardi, Alessia Sutherland, C. Tom Cole, Adam R. |
| Copyright Year | 2011 |
| Abstract | Collapsin response mediator protein 2 (CRMP2) is an abundant brain-enriched protein that regulates neurite outgrowth. It is phosphorylated by Cdk5 and GSK3, and these modifications are abnormally high in the brains of Alzheimer's disease (AD) patients. Increased phosphorylation of CRMP2 is also apparent in mouse models of AD that express mutated AβPP and PSEN1, but not AβPP or tau alone, where it is detectable before the appearance of amyloid plaques and neurofibrillary tangles, suggesting it is an early event in AD pathogenesis. Here, we have extended these observations by showing that CRMP2 is not hyperphosphorylated in mice overexpressing mutated PSEN1 alone, or in cultured neurons treated with soluble, oligomeric Aβ42 peptide. Similarly, CRMP2 phosphorylation was not increased in a mouse model of severe neurodegeneration (PMSC-1 knockout) or in cultured neurons subjected to neurotoxic concentrations of NMDA or staurosporine. Most interestingly, CRMP2 phosphorylation was not increased in frontal cortex from patients with frontotemporal lobar degeneration associated with mutations in MAPT or with Pick bodies. Together, these observations are consistent with the hypothesis that abnormal phosphorylation of CRMP2 is specific to AD and occurs downstream of excessive processing of AβPP, but that neither excessive Aβ42 peptide nor neurotoxicity alone are sufficient to promote hyperphosphorylation. |
| Starting Page | 89 |
| Ending Page | 96 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.j-alz.com/issues/27/williamson_supplement.pdf |
| PubMed reference number | 21860090v1 |
| Alternate Webpage(s) | https://doi.org/10.3233/JAD-2011-110617 |
| DOI | 10.3233/jad-2011-110617 |
| Journal | Journal of Alzheimer's disease : JAD |
| Volume Number | 27 |
| Issue Number | 3 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Alzheimer's Disease Brain DPYSL2 gene Frontotemporal Lobar Degeneration Glycogen Synthase Kinase 3 Mediator brand of benfluorex hydrochloride Mutation N-Methylaspartate Nerve Degeneration Neurodegenerative Disorders Neurofibrillary degeneration (morphologic abnormality) Neuronal Outgrowth Neurotoxicity Syndromes PSEN1 gene Patients Peptide PHI Semaphorin-3A Senile Plaques Staurosporine frontal lobe negative regulation of phosphorylation of RNA polymerase II C-terminal domain |
| Content Type | Text |
| Resource Type | Article |
