Shortfalls in the peptidyl-prolyl cis-trans isomerase protein Pin1 in neurons are associated with frontotemporal dementias

Thorpe, JR, Mosaheb, S, Hashemzadeh-Bonehi, L, Cairns, NJ, Kay, JE, Morley, SJ and Rulten, SL (2004) Shortfalls in the peptidyl-prolyl cis-trans isomerase protein Pin1 in neurons are associated with frontotemporal dementias. Neurobiology of Disease, 17 (2). pp. 237-249. ISSN 0969-9961

Full text not available from this repository.

Abstract

The peptidyl-prolyl cis-trans isomerase (PPIase) Pin1 modulates the activity of a range of target proteins involved in the cell cycle, transcription, translation, endocytosis, and apoptosis by facilitating dephosphorylation of phosphorylated serine or threonine residue preceding a proline (p-Ser/Thr-Pro) motifs catalyzed by phosphatases specific for the trans conformations. Pin1 targets include the neuronal microtubule-associated protein tau, whose dephosphorylation restores its ability to stabilize microtubules. We, and others, have shown that tau hyperphosphorylation in the neurofibrillary tangles (NFTs) of Alzheimer disease (AD) is associated with redirection of the predominantly nuclear Pin1 to the cytoplasm and with Pin1 shortfalls throughout subcellular compartments. As nuclear Pin1 depletion causes apoptosis, shortfalls in regard to both nuclear and p-tau targets may contribute to neuronal dysfunction. We report here that similar Pin1 redistribution and shortfalls occur in frontotemporal dementias (FTDs) characterized by abnormal protein aggregates of tau and other cytoskeletal proteins. This may be a unifying, contributory factor towards neuronal death in these dementias.

Item Type: Article
Schools and Departments: School of Life Sciences
Brighton and Sussex Medical School > Brighton and Sussex Medical School
School of Life Sciences > Biochemistry
Subjects: R Medicine > RB Pathology
Q Science > QP Physiology
Depositing User: Stuart Rulten
Date Deposited: 11 Dec 2006
Last Modified: 30 Nov 2012 16:50
URI: http://sro.sussex.ac.uk/id/eprint/633
Google Scholar:25 Citations
📧 Request an update