Advances in Alzheimer's Research

Volume: 2

Indexed in: EBSCO, Ulrich's Periodicals Directory

Alzheimer’s disease (AD) is currently recognized as an untreatable, progressive, degenerative and terminal disease that is global – afflicting over 36 million people worldwide, with the number ...
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Increased CRMP-2 Phosphorylation is Observed in Alzheimer’s Disease: Does This Tell Anything about Disease Development?

Pp. 148-170 (23)

Marc P.M. Soutar, Paul Thornhill, Adam R. Cole and Calum Sutherland

Abstract

Collapsin response mediator protein-2 (CRMP-2) is a physiological substrate for GSK3 and Cdk5, two protein kinases suggested to exhibit greater activity in Alzheimer’s disease (AD). Indeed, phosphorylation of CRMP-2, at the residues targeted by GSK3 and Cdk5, is relatively high in cortex isolated from human AD brain, as well as in the brains of animal models of AD, while phospho-CRMP-2 is found in neurofibrillary tangles. In mouse models of AD, increased phosphorylation occurs prior to pathology, and abnormal phosphorylation is not seen in other forms of human dementia. Although CRMP-2 has no known enzymatic activity, a great deal of information is appearing on its importance in neuronal development and polarity, as well as in axon growth and guidance. In this mini-review, we examine what is known about CRMP-2 function, how that is controlled by phosphorylation, what alterations in molecular mechanisms could lead to the abnormally high CRMP-2 phosphorylation in AD, and whether this is likely to be specific to AD or occur in other forms of neurodegeneration. This will include discussion of the evidence for increased GSK3 or Cdk5 activity, for decreased phosphatase activity, or the upregulation of other CRMP-2 protein kinases in AD. Importantly, we will compare the processes that may contribute to increased CRMP-2 phosphorylation with those known to increase tau hyperphosphorylation in AD, and whether these are likely to be part of disease development or a useful early marker for AD.

Keywords:

Biomarker, collapsin response mediator protein, microtubule transport, neuronal polarity, phosphorylation.

Affiliation:

Medical Research Institute, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, Scotland, United Kingdom.