Metabotropic Glutamate Receptors in Alzheimer's Disease Synaptic Dysfunction: Therapeutic Opportunities and Hope for the Future

J Alzheimers Dis. 2020;78(4):1345-1361. doi: 10.3233/JAD-201146.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of neuritic plaques and neurofibrillary tangles. The impaired synaptic plasticity and dendritic loss at the synaptic level is an early event associated with the AD pathogenesis. The abnormal accumulation of soluble oligomeric amyloid-β (Aβ), the major toxic component in amyloid plaques, is viewed to trigger synaptic dysfunctions through binding to several presynaptic and postsynaptic partners and thus to disrupt synaptic transmission. Over time, the abnormalities in neural transmission will result in cognitive deficits, which are commonly manifested as memory loss in AD patients. Synaptic plasticity is regulated through glutamate transmission, which is mediated by various glutamate receptors. Here we review recent progresses in the study of metabotropic glutamate receptors (mGluRs) in AD cognition. We will discuss the role of mGluRs in synaptic plasticity and their modulation as a possible strategy for AD cognitive improvement.

Keywords: Alzheimer’s disease; cognition; ionotropic glutamate receptors; long term depression; long term potentiation; metabotropic glutamate receptors; synapse; synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism*
  • Humans
  • Neuronal Plasticity*
  • Receptors, Metabotropic Glutamate / metabolism*
  • Receptors, Metabotropic Glutamate / physiology
  • Synapses / metabolism*

Substances

  • Amyloid beta-Peptides
  • Receptors, Metabotropic Glutamate