May 2, 2017

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

Neural Plasticity
Lingyan XuYuesong Gong

Abstract

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 asβ-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 Aβand to excitation, thereby inhibiting NMDA receptor-mediated synaptic plasticity and exacerbating NMDA receptor-mediated synaptic degeneration. These results suggest th...Continue Reading

  • References
  • Citations1

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations1

Citations

Mentioned in this Paper

Cell Cycle Progression
Familial Alzheimer Disease (FAD)
Proteasome Pathway
PIN1 gene
Abnormal Degeneration
APP protein, human
PIN1
Ubiquitin
Memory Impairment
Postsynaptic Density Organization

Related Feeds

Alzheimer's Disease: Abeta

Alzheimer's disease (AD) is a chronic neurodegenerative disease associated with accumulation of amyloid plaques, which are comprised of amyloid beta. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques. Here is the latest research.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a chronic neurodegenerative disease. This feed focuses on the underlying role of Tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's.