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CRMP2 Hyperphosphorylation is Characteristic of Alzheimer's Disease and not a Feature Common to Other Neurodegenerative Diseases
- Source :
- Journal of Alzheimer's Disease. 27:615-625
- Publication Year :
- 2011
- Publisher :
- IOS Press, 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.
- Subjects :
- Male
Molecular Sequence Data
Hyperphosphorylation
Mice, Transgenic
Nerve Tissue Proteins
Biology
Rats, Sprague-Dawley
Mice
Alzheimer Disease
medicine
PSEN1
Animals
Humans
Amino Acid Sequence
Phosphorylation
Cells, Cultured
Aged
Aged, 80 and over
Mice, Knockout
Sheep
General Neuroscience
Cyclin-dependent kinase 5
Neurodegeneration
Neurotoxicity
Neurodegenerative Diseases
General Medicine
Frontotemporal lobar degeneration
Middle Aged
medicine.disease
Cell biology
Disease Models, Animal
Psychiatry and Mental health
Clinical Psychology
Animals, Newborn
Tauopathies
Intercellular Signaling Peptides and Proteins
Female
Collapsin response mediator protein family
Geriatrics and Gerontology
Alzheimer's disease
Neuroscience
Subjects
Details
- ISSN :
- 18758908 and 13872877
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Journal of Alzheimer's Disease
- Accession number :
- edsair.doi.dedup.....0b15908c480c165f425fb48b6209bf51
- Full Text :
- https://doi.org/10.3233/jad-2011-110617