Abstract
Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans conversion of phosphorylated proteins at serine or threonine residues which precede a proline. The peptidyl-prolyl isomerization induces a conformational change of the proteins involved in cell signaling process. Pin1 dysregulation has been associated with some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Proline-directed phosphorylation is a common regulator of these pathologies and a recent work showed that it is also involved in prion disorders. In fact, prion protein phosphorylation at the Ser-43-Pro motif induces prion protein conversion into a disease-associated form. Furthermore, phosphorylation at Ser-43-Pro has been observed to increase in the cerebral spinal fluid of sporadic Creutzfeldt-Jakob Disease patients. These findings provide new insights into the pathogenesis of prion disorders, suggesting Pin1 as a potential new player in the disease. In this paper, we review the mechanisms underlying Pin1 involvement in the aforementioned neurodegenerative pathologies focusing on the potential role of Pin1 in prion disorders.
Highlights
Proline-directed protein phosphorylation is a key event in the regulation of cell signaling that has gained attention thanks to the recent discovery of Pin1, a member of the peptidyl-prolyl cis/trans isomerase (PPIase) family
We review Pin1 involvement in neurodegenerative pathologies focusing on the potential impact of this PPIase in the development of prion disorders
In this review we discussed the state of the art concerning the role of Pin1 in neurodegenerative disorders
Summary
Proline-directed protein phosphorylation is a key event in the regulation of cell signaling that has gained attention thanks to the recent discovery of Pin, a member of the peptidyl-prolyl cis/trans isomerase (PPIase) family. In Alzheimer’s disease (AD), aberrant amyloid precursor protein (APP) and tau phosphorylation occurs, leading to extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs) formation made of toxic amyloid-beta peptides and hyperphosphorylated tau, respectively. The accumulation of these deposits causes synaptic dysfunction and loss of neurons [5]. Phosphorylation of prion protein at Ser-43-Pro induces the formation of proteinase K resistant aggregates in vivo [12] This result suggests that Pin could have a crucial function in AD, PD, and HD, and in prion disorders. We review Pin involvement in neurodegenerative pathologies focusing on the potential impact of this PPIase in the development of prion disorders
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