Amyloid-β-Induced Dysregulation of AMPA Receptor Trafficking.

Abstract:

:Evidence from neuropathological, genetic, animal model, and biochemical studies has indicated that the accumulation of amyloid-beta (Aβ) is associated with, and probably induces, profound neuronal changes in brain regions critical for memory and cognition in the development of Alzheimer's disease (AD). There is considerable evidence that synapses are particularly vulnerable to AD, establishing synaptic dysfunction as one of the earliest events in pathogenesis, prior to neuronal loss. It is clear that excessive Aβ levels can disrupt excitatory synaptic transmission and plasticity, mainly due to dysregulation of the AMPA and NMDA glutamate receptors in the brain. Importantly, AMPA receptors are the principal glutamate receptors that mediate fast excitatory neurotransmission. This is essential for synaptic plasticity, a cellular correlate of learning and memory, which are the cognitive functions that are most disrupted in AD. Here we review recent advances in the field and provide insights into the molecular mechanisms that underlie Aβ-induced dysfunction of AMPA receptor trafficking. This review focuses primarily on NMDA receptor- and metabotropic glutamate receptor-mediated signaling. In particular, we highlight several mechanisms that underlie synaptic long-term depression as common signaling pathways that are hijacked by the neurotoxic effects of Aβ.

journal_name

Neural Plast

journal_title

Neural plasticity

authors

Guntupalli S,Widagdo J,Anggono V

doi

10.1155/2016/3204519

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

3204519

eissn

2090-5904

issn

1687-5443

journal_volume

2016

pub_type

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