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Pathological Role of Peptidyl-Prolyl Isomerase Pin1 in the Disruption of Synaptic Plasticity in Alzheimer's Disease
Journal article   Open access   Peer reviewed

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

Lingyan Xu, Zhiyun Ren, Frances E Chow, Richard Tsai, Tongzheng Liu, Flavio Rizzolio, Silvia Boffo, Yungen Xu, Shaohui Huang, Carol F Lippa, …
Neural plasticity, v 2017, p12
2017
DOI: https://doi.org/10.1155/2017/3270725
PMID: 28458925
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1155/2017/3270725View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Aged Aged, 80 and over Alzheimer Disease - metabolism Alzheimer Disease - pathology Amyloid beta-Peptides - metabolism Animals Brain - metabolism Brain - pathology Cells, Cultured Dendritic Spines - metabolism Dendritic Spines - pathology Disks Large Homolog 4 Protein - metabolism Humans Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Nerve Tissue Proteins - metabolism Neuronal Plasticity NIMA-Interacting Peptidylprolyl Isomerase - genetics NIMA-Interacting Peptidylprolyl Isomerase - metabolism Phosphorylation Post-Synaptic Density - metabolism Post-Synaptic Density - pathology Receptors, N-Methyl-D-Aspartate - metabolism tau Proteins - metabolism Ubiquitin - metabolism
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 -amyloid (A ) 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 A 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.

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Domestic collaboration
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Web of Science research areas
Neurosciences
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