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Neural Plasticity
Volume 2017, Article ID 3270725, 12 pages
Research Article

Pathological Role of Peptidyl-Prolyl Isomerase Pin1 in the Disruption of Synaptic Plasticity in Alzheimer’s Disease

1Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, Department of Biopharmaceutics and Food Science, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
2Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19102, USA
3Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA
4Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA 19122, USA
5Department of Molecular Science and Nanosystems, Ca’ Foscari Università di Venezia, Via Torino 155, 30172 Venezia-Mestre, Italy
6Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China
7Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

Correspondence should be addressed to Carol F. Lippa; ude.demlexerd@appil.lorac and Yuesong Gong; nc.ude.mcujn@gnogy

Received 28 October 2016; Accepted 12 December 2016; Published 26 March 2017

Academic Editor: Jason Huang

Copyright © 2017 Lingyan Xu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Synaptic loss is the structural basis for memory impairment in Alzheimer’s disease (AD). While the underlying pathological mechanism remains elusive, it is known that misfolded proteins accumulate as β-amyloid (Aβ) plaques and hyperphosphorylated Tau tangles decades before the onset of clinical disease. The loss of Pin1 facilitates the formation of these misfolded proteins in AD. Pin1 protein controls cell-cycle progression and determines the fate of proteins by the ubiquitin proteasome system. The activity of the ubiquitin proteasome system directly affects the functional and structural plasticity of the synapse. We localized Pin1 to dendritic rafts and postsynaptic density (PSD) and found the pathological loss of Pin1 within the synapses of AD brain cortical tissues. The loss of Pin1 activity may alter the ubiquitin-regulated modification of PSD proteins and decrease levels of Shank protein, resulting in aberrant synaptic structure. The loss of Pin1 activity, induced by oxidative stress, may also render neurons more susceptible to the toxicity of oligomers of Aβ and to excitation, thereby inhibiting NMDA receptor-mediated synaptic plasticity and exacerbating NMDA receptor-mediated synaptic degeneration. These results suggest that loss of Pin1 activity could lead to the loss of synaptic plasticity in the development of AD.