Targeting the NMDA receptor subunit NR2B for treating or preventing age-related memory decline

Deheng Wang, Stephanie A. Jacobs, Joseph Zhuo Tsien

Research output: Contribution to journalReview article

23 Citations (Scopus)

Abstract

Introduction: Age-related memory loss is believed to be a result of reduced synaptic plasticity, including changes in the NR2 subunit composition of the NMDA receptor. It is known that endogenous NR2B subunits decrease as the brain ages, whereas transgenic upregulation of NR2B enhances synaptic plasticity and learning and memory in several animal species. Accumulating evidence suggests that elevated brain magnesium levels, via dietary supplementation, can boost NR2B in the brain, consequently reversing memory deficits and enhancing cognitive abilities.Areas covered: This review highlights the convergent molecular mechanisms via the NR2B pathway as a useful strategy for treating age-related memory loss. A dietary approach, via oral intake of a novel compound, magnesium L-threonate (MgT), to boost NR2B expression in the brain is highlighted.Expert opinion: Direct upregulation of the NR2B subunit expression can enhance synaptic plasticity and memory functions in a broad range of behavioral tasks in rodents. Other upregulation approaches, such as targeting the NR2B transporter or surface recycling pathway via cyclin-dependent kinase 5, are highly effective in improving memory functions. A dietary supplemental approach by optimally elevating the [Mg2+] in the brain is surprisingly effective in upregulating NR2B expression and improving memories in preclinical studies. MgT is currently under clinical trials.

Original languageEnglish (US)
Pages (from-to)1121-1130
Number of pages10
JournalExpert Opinion on Therapeutic Targets
Volume18
Issue number10
DOIs
StatePublished - Oct 1 2014

Fingerprint

N-Methyl-D-Aspartate Receptors
Neuronal Plasticity
Memory Disorders
Data storage equipment
Brain
Up-Regulation
Plasticity
Cyclin-Dependent Kinase 5
Magnesium
Magnesium Compounds
Aptitude
Expert Testimony
Dietary Supplements
Rodentia
NR2B NMDA receptor
Clinical Trials
Learning
Recycling
Animals
Chemical analysis

Keywords

  • Age-related memory loss
  • Alzheimer
  • Depression
  • Magnesium
  • Magnesium L-threonate
  • Memory enhancement
  • Mild cognitive impairment
  • NMDA receptor NR2B
  • NMDA receptors
  • Parkinson
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Targeting the NMDA receptor subunit NR2B for treating or preventing age-related memory decline. / Wang, Deheng; Jacobs, Stephanie A.; Tsien, Joseph Zhuo.

In: Expert Opinion on Therapeutic Targets, Vol. 18, No. 10, 01.10.2014, p. 1121-1130.

Research output: Contribution to journalReview article

@article{74849246c400482f85e0227e2643a03b,
title = "Targeting the NMDA receptor subunit NR2B for treating or preventing age-related memory decline",
abstract = "Introduction: Age-related memory loss is believed to be a result of reduced synaptic plasticity, including changes in the NR2 subunit composition of the NMDA receptor. It is known that endogenous NR2B subunits decrease as the brain ages, whereas transgenic upregulation of NR2B enhances synaptic plasticity and learning and memory in several animal species. Accumulating evidence suggests that elevated brain magnesium levels, via dietary supplementation, can boost NR2B in the brain, consequently reversing memory deficits and enhancing cognitive abilities.Areas covered: This review highlights the convergent molecular mechanisms via the NR2B pathway as a useful strategy for treating age-related memory loss. A dietary approach, via oral intake of a novel compound, magnesium L-threonate (MgT), to boost NR2B expression in the brain is highlighted.Expert opinion: Direct upregulation of the NR2B subunit expression can enhance synaptic plasticity and memory functions in a broad range of behavioral tasks in rodents. Other upregulation approaches, such as targeting the NR2B transporter or surface recycling pathway via cyclin-dependent kinase 5, are highly effective in improving memory functions. A dietary supplemental approach by optimally elevating the [Mg2+] in the brain is surprisingly effective in upregulating NR2B expression and improving memories in preclinical studies. MgT is currently under clinical trials.",
keywords = "Age-related memory loss, Alzheimer, Depression, Magnesium, Magnesium L-threonate, Memory enhancement, Mild cognitive impairment, NMDA receptor NR2B, NMDA receptors, Parkinson, Schizophrenia",
author = "Deheng Wang and Jacobs, {Stephanie A.} and Tsien, {Joseph Zhuo}",
year = "2014",
month = "10",
day = "1",
doi = "10.1517/14728222.2014.941286",
language = "English (US)",
volume = "18",
pages = "1121--1130",
journal = "Expert Opinion on Therapeutic Targets",
issn = "1472-8222",
publisher = "Informa Healthcare",
number = "10",

}

TY - JOUR

T1 - Targeting the NMDA receptor subunit NR2B for treating or preventing age-related memory decline

AU - Wang, Deheng

AU - Jacobs, Stephanie A.

AU - Tsien, Joseph Zhuo

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Introduction: Age-related memory loss is believed to be a result of reduced synaptic plasticity, including changes in the NR2 subunit composition of the NMDA receptor. It is known that endogenous NR2B subunits decrease as the brain ages, whereas transgenic upregulation of NR2B enhances synaptic plasticity and learning and memory in several animal species. Accumulating evidence suggests that elevated brain magnesium levels, via dietary supplementation, can boost NR2B in the brain, consequently reversing memory deficits and enhancing cognitive abilities.Areas covered: This review highlights the convergent molecular mechanisms via the NR2B pathway as a useful strategy for treating age-related memory loss. A dietary approach, via oral intake of a novel compound, magnesium L-threonate (MgT), to boost NR2B expression in the brain is highlighted.Expert opinion: Direct upregulation of the NR2B subunit expression can enhance synaptic plasticity and memory functions in a broad range of behavioral tasks in rodents. Other upregulation approaches, such as targeting the NR2B transporter or surface recycling pathway via cyclin-dependent kinase 5, are highly effective in improving memory functions. A dietary supplemental approach by optimally elevating the [Mg2+] in the brain is surprisingly effective in upregulating NR2B expression and improving memories in preclinical studies. MgT is currently under clinical trials.

AB - Introduction: Age-related memory loss is believed to be a result of reduced synaptic plasticity, including changes in the NR2 subunit composition of the NMDA receptor. It is known that endogenous NR2B subunits decrease as the brain ages, whereas transgenic upregulation of NR2B enhances synaptic plasticity and learning and memory in several animal species. Accumulating evidence suggests that elevated brain magnesium levels, via dietary supplementation, can boost NR2B in the brain, consequently reversing memory deficits and enhancing cognitive abilities.Areas covered: This review highlights the convergent molecular mechanisms via the NR2B pathway as a useful strategy for treating age-related memory loss. A dietary approach, via oral intake of a novel compound, magnesium L-threonate (MgT), to boost NR2B expression in the brain is highlighted.Expert opinion: Direct upregulation of the NR2B subunit expression can enhance synaptic plasticity and memory functions in a broad range of behavioral tasks in rodents. Other upregulation approaches, such as targeting the NR2B transporter or surface recycling pathway via cyclin-dependent kinase 5, are highly effective in improving memory functions. A dietary supplemental approach by optimally elevating the [Mg2+] in the brain is surprisingly effective in upregulating NR2B expression and improving memories in preclinical studies. MgT is currently under clinical trials.

KW - Age-related memory loss

KW - Alzheimer

KW - Depression

KW - Magnesium

KW - Magnesium L-threonate

KW - Memory enhancement

KW - Mild cognitive impairment

KW - NMDA receptor NR2B

KW - NMDA receptors

KW - Parkinson

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=84907062342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907062342&partnerID=8YFLogxK

U2 - 10.1517/14728222.2014.941286

DO - 10.1517/14728222.2014.941286

M3 - Review article

C2 - 25152202

AN - SCOPUS:84907062342

VL - 18

SP - 1121

EP - 1130

JO - Expert Opinion on Therapeutic Targets

JF - Expert Opinion on Therapeutic Targets

SN - 1472-8222

IS - 10

ER -