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The emerging role of peptidyl-prolyl isomerase chaperones in tau oligomerization,
amyloid processing, and Alzheimer s disease
#MMPMID25628064
Blair LJ
; Baker JD
; Sabbagh JJ
; Dickey CA
J Neurochem
2015[Apr]; 133
(1
): 1-13
PMID25628064
show ga
Peptidyl-prolyl cis/trans isomerases (PPIases), a unique family of molecular
chaperones, regulate protein folding at proline residues. These residues are
abundant within intrinsically disordered proteins, like the
microtubule-associated protein tau. Tau has been shown to become
hyperphosphorylated and accumulate as one of the two main pathological hallmarks
in Alzheimer's disease, the other being amyloid beta (Ab). PPIases, including
Pin1, FK506-binding protein (FKBP) 52, FKBP51, and FKBP12, have been shown to
interact with and regulate tau biology. This interaction is particularly
important given the numerous proline-directed phosphorylation sites found on tau
and the role phosphorylation has been found to play in pathogenesis. This
regulation then affects downstream aggregation and oligomerization of tau.
However, many PPIases have yet to be explored for their effects on tau biology,
despite the high likelihood of interaction based on proline content. Moreover,
Pin1, FKBP12, FKBP52, cyclophilin (Cyp) A, CypB, and CypD have been shown to also
regulate Ab production or the toxicity associated with Ab pathology. Therefore,
PPIases directly and indirectly regulate pathogenic protein multimerization in
Alzheimer's disease and represent a family rich in targets for modulating the
accumulation and toxicity.
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