NMDARs Adapt to Neurotoxic HIV Protein Tat Downstream of a GluN2A-Ubiquitin Ligase Signaling Pathway

Overview

Journal J Neurosci

Specialty Neurology

Date 2016 Nov 5

PMID 27810933

Citations 15

Authors

Matthew V Green

Stanley A Thayer

Affiliations

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Abstract

Significance Statement: Synaptodendritic damage correlates with cognitive decline in HIV-associated neurocognitive disorder (HAND). In a cell culture model, we show that the HIV protein transactivator of transcription (Tat) initially potentiates NMDARs that then adapt to the presence of the toxin. Adaptation of NMDAR function was mediated by a GluN2A/Akt/Mdm2 pathway not previously linked to neuroinflammatory disorders such as HAND. Activation of this pathway caused a loss of synaptic NMDAR clusters. Decreased NMDAR function may result from a homeostatic response gone awry and underlie impaired synaptic function in HAND.

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