Pin1 and neurodegeneration: a new player for prion disorders?

Elisa Isopi; Giuseppe Legname; Elisa Isopi; Giuseppe Legname

doi:10.3934/molsci.2015.3.311

AIMS Molecular Science

2015, Volume 2, Issue 3: 311-323. doi: 10.3934/molsci.2015.3.311

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Review Special Issues

Pin1 and neurodegeneration: a new player for prion disorders?

Elisa Isopi ¹,
Giuseppe Legname ^{1,2
,
,}

1.
Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy;
2.
ELETTRA- Sincrotrone Trieste S.C.p.A, Trieste, Italy

Received: 14 April 2015 Accepted: 03 July 2015 Published: 09 July 2015

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.
- Pin1,
- Alzheimer's disease,
- Parkinson's disease,
- Huntington's disease,
- prion diseases
Citation: Elisa Isopi, Giuseppe Legname. Pin1 and neurodegeneration: a new player for prion disorders?[J]. AIMS Molecular Science, 2015, 2(3): 311-323. doi: 10.3934/molsci.2015.3.311

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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.

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