scholarly journals Enhancing NMDA Receptor Function: Recent Progress on Allosteric Modulators

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Lulu Yao ◽  
Qiang Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Recent Progress ◽  
Brain Diseases ◽  
Allosteric Modulators ◽  
Receptor Function ◽  
Nmda Receptor Function ◽  
Excitatory Neurotransmission

The N-methyl-D-aspartate receptors (NMDARs) are subtype glutamate receptors that play important roles in excitatory neurotransmission and synaptic plasticity. Their hypo- or hyperactivation are proposed to contribute to the genesis or progression of various brain diseases, including stroke, schizophrenia, depression, and Alzheimer’s disease. Past efforts in targeting NMDARs for therapeutic intervention have largely been on inhibitors of NMDARs. In light of the discovery of NMDAR hypofunction in psychiatric disorders and perhaps Alzheimer’s disease, efforts in boosting NMDAR activity/functions have surged in recent years. In this review, we will focus on enhancing NMDAR functions, especially on the recent progress in the generation of subunit-selective, allosteric positive modulators (PAMs) of NMDARs. We shall also discuss the usefulness of these newly developed NMDAR-PAMs.

Preconceptions and prerequisites: Understanding the function of synaptic plasticity will also depend on a better systems-level understanding of the multiple types of memory

1997 ◽  
Vol 20 (4) ◽  
pp. 624-625 ◽  
Author(s):  
Richard G. M. Morris
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Nmda Receptor ◽  
Receptor Function ◽  
Relevant Evidence ◽  
Learning Hypothesis ◽  
Nmda Receptor Function

Although it is not their fault, Shors & Matzel's attempt to review the LTP and learning hypothesis suffers from there being no clear published statement of the idea. Their summary of relevant evidence is not without error, however, and it oversimplifies fundamental issues relating to NMDA receptor function. Their attentional hypothesis is intriguing but requires a better systems-level understanding of how attention contributes to cognitive function.

scholarly journals Protein kinase A-dependent enhanced NMDA receptor function in pain-related synaptic plasticity in rat amygdala neurones

2005 ◽  
Vol 564 (3) ◽  
pp. 907-921 ◽  
Author(s):  
Gary C. Bird ◽  
L. Leanne Lash ◽  
Jeong S. Han ◽  
Xiaoju Zou ◽  
William D. Willis ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Receptor Function ◽  
Nmda Receptor Function ◽  
Kinase A

Effect of transgenic overexpression of NR2B on NMDA receptor function and synaptic plasticity in visual cortex

2001 ◽  
Vol 41 (6) ◽  
pp. 762-770 ◽  
Author(s):  
Benjamin D. Philpot ◽  
Michael P. Weisberg ◽  
Margarita S. Ramos ◽  
Nathaniel B. Sawtell ◽  
Ya-Ping Tang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Visual Cortex ◽  
Nmda Receptor ◽  
Receptor Function ◽  
Nmda Receptor Function

scholarly journals A novel class of negative allosteric modulators of NMDA receptor function

2015 ◽  
Vol 25 (23) ◽  
pp. 5583-5588 ◽  
Author(s):  
Brooke M. Katzman ◽  
Riley E. Perszyk ◽  
Hongjie Yuan ◽  
Yesim Altas Tahirovic ◽  
Ayodeji E. Sotimehin ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Allosteric Modulators ◽  
Receptor Function ◽  
Nmda Receptor Function

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

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Lingyan Xu ◽  
Zhiyun Ren ◽  
Frances E. Chow ◽  
Richard Tsai ◽  
Tongzheng Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Cell Cycle Progression ◽  
Ubiquitin Proteasome System ◽  
Misfolded Proteins ◽  
Structural Basis ◽  
Amyloid A ◽  
Ubiquitin Proteasome

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.

Sign in / Sign up

Export Citation Format

Share Document