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Review
. 2011 Aug;44(1):65-70.
doi: 10.1007/s12035-011-8182-4. Epub 2011 Apr 28.

Bending tau into shape: the emerging role of peptidyl-prolyl isomerases in tauopathies

John Koren 3rd  1 , Umesh K Jinwal, Zachary Davey, Janine Kiray, Karthik Arulselvam, Chad A Dickey
Affiliations
Review

Bending tau into shape: the emerging role of peptidyl-prolyl isomerases in tauopathies

John Koren 3rd et al. Mol Neurobiol. 2011 Aug.

Abstract

The Hsp90-associated cis-trans peptidyl-prolyl isomerase--FK506 binding protein 51 (FKBP51)--was recently found to co-localize with the microtubule (MT)-associated protein tau in neurons and physically interact with tau in brain tissues from humans who died from Alzheimer's disease (AD). Tau pathologically aggregates in neurons, a process that is closely linked with cognitive deficits in AD. Tau typically functions to stabilize and bundle MTs. Cellular events like calcium influx destabilize MTs, disengaging tau. This excess tau should be degraded, but sometimes it is stabilized and forms higher-order aggregates, a pathogenic hallmark of tauopathies. FKBP51 was also found to increase in forebrain neurons with age, further supporting a novel role for FKBP51 in tau processing. This, combined with compelling evidence that the prolyl isomerase Pin1 regulates tau stability and phosphorylation dynamics, suggests an emerging role for isomerization in tau pathogenesis.

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Figures

Figure 1
Figure 1. PPIases isomerize tau within its proline-rich region to regulate tau phosphorylation dynamics
The proline-rich region of tau, which spans amino acids 231 to 255, contains a number of Ser/Thr phosphorylation sites that have been implicated in disease. Both CdK5 and GSK3β phosphorylate tau at proline-directed Ser/Thr sites and phosphatases can also remove these phosphate motifs. Thus, PPIases may play a critical part in regulating phosphorylation dynamics of tau.
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