Calcyclin binding protein and Siah-1 interacting protein in Alzheimer’s disease pathology: neuronal localization and possible function

In this work we have studied the role of CacyBP/SIP in Alzheimer’s disease which belongs to a group of neurodegenerative diseases collectively designated as ‘‘tauopathies’’. They are characterized by the aggregation of abnormally phosphorylated tau protein which leads to formation of PHFs (paired helical filaments) or NFTs (neurofibrillary tangles) and in consequence, cause the pathology. The CacyBP/SIP protein is highly expressed in brain and its interaction with tubulin suggested involvement of this protein in cytoskeletal reorganization which is important in many cellular processes occurring during neurodegeneration. In this work we have shown, using brain tissue from Alzheimer disease (AD) patients and from transgenic mice modeling human tauopathy, that CacyBP/SIP co-localizes with PHF in neurons of AD brains and exhibits similar subcellular localization as tau protein in neurons of tauopathic mice brains. Moreover, our results have shown for the first time that CacyBP/SIP might dephosphorylate tau protein. This finding seems to be important in future studies concerning the understanding of molecular mechanisms leading to AD pathology.

Date of publication
15 April 2013