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Int. J. Mol. Sci. 2018, 19(8), 2319; https://doi.org/10.3390/ijms19082319

Pin1 Modulation in Physiological Status and Neurodegeneration. Any Contribution to the Pathogenesis of Type 3 Diabetes?

Research Unit for Multi-factorial Diseases, Obesity and Diabetes, Bambino Gesù Children’s Hospital IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), viale di San Paolo 15, 00146 Rome, Italy
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Received: 27 June 2018 / Revised: 3 August 2018 / Accepted: 6 August 2018 / Published: 8 August 2018
(This article belongs to the Special Issue Molecular Mechanism of Alzheimer's Disease)
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Abstract

Prolyl isomerases (Peptidylprolyl isomerase, PPIases) are enzymes that catalyze the isomerization between the cis/trans Pro conformations. Three subclasses belong to the class: FKBP (FK506 binding protein family), Cyclophilin and Parvulin family (Pin1 and Par14). Among Prolyl isomerases, Pin1 presents as distinctive feature, the ability of binding to the motif pSer/pThr-Pro that is phosphorylated by kinases. Modulation of Pin1 is implicated in cellular processes such as mitosis, differentiation and metabolism: The enzyme is dysregulated in many diverse pathological conditions, i.e., cancer progression, neurodegenerative (i.e., Alzheimer’s diseases, AD) and metabolic disorders (i.e., type 2 diabetes, T2D). Indeed, Pin1 KO mice develop a complex phenotype of premature aging, cognitive impairment in elderly mice and neuronal degeneration resembling that of the AD in humans. In addition, since the molecule modulates glucose homeostasis in the brain and peripherally, Pin1 KO mice are resistant to diet-induced obesity, insulin resistance, peripheral glucose intolerance and diabetic vascular dysfunction. In this review, we revise first critically the role of Pin1 in neuronal development and differentiation and then focus on the in vivo studies that demonstrate its pivotal role in neurodegenerative processes and glucose homeostasis. We discuss evidence that enables us to speculate about the role of Pin1 as molecular link in the pathogenesis of type 3 diabetes i.e., the clinical association of dementia/AD and T2D. View Full-Text
Keywords: Alzheimer’s disease; brain glucose metabolism; neuronal differentiation; neuronal degeneration; Prolyl isomerases; Pin1; type 2 diabetes; type 3 diabetes Alzheimer’s disease; brain glucose metabolism; neuronal differentiation; neuronal degeneration; Prolyl isomerases; Pin1; type 2 diabetes; type 3 diabetes
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Bianchi, M.; Manco, M. Pin1 Modulation in Physiological Status and Neurodegeneration. Any Contribution to the Pathogenesis of Type 3 Diabetes? Int. J. Mol. Sci. 2018, 19, 2319.

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