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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2011

Open Access 01-12-2011 | Review

Flipping the switches: CD40 and CD45 modulation of microglial activation states in HIV associated dementia (HAD)

Authors: Jon Salemi, Demian F Obregon, Anthony Cobb, Spenser Reed, Edin Sadic, Jingji Jin, Francisco Fernandez, Jun Tan, Brian Giunta

Published in: Molecular Neurodegeneration | Issue 1/2011

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Abstract

Microglial dysfunction is associated with the pathogenesis and progression of a number of neurodegenerative disorders including HIV associated dementia (HAD). HIV promotion of an M1 antigen presenting cell (APC) - like microglial phenotype, through the promotion of CD40 activity, may impair endogenous mechanisms important for amyloid- beta (Aβ) protein clearance. Further, a chronic pro-inflammatory cycle is established in this manner. CD45 is a protein tyrosine phosphatase receptor which negatively regulates CD40L-CD40-induced microglial M1 activation; an effect leading to the promotion of an M2 phenotype better suited to phagocytose and clear Aβ. Moreover, this CD45 mediated activation state appears to dampen harmful cytokine production. As such, this property of microglial CD45 as a regulatory "off switch" for a CD40-promoted M1, APC-type microglia activation phenotype may represent a critical therapeutic target for the prevention and treatment of neurodegeneration, as well as microglial dysfunction, found in patients with HAD.
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Metadata
Title
Flipping the switches: CD40 and CD45 modulation of microglial activation states in HIV associated dementia (HAD)
Authors
Jon Salemi
Demian F Obregon
Anthony Cobb
Spenser Reed
Edin Sadic
Jingji Jin
Francisco Fernandez
Jun Tan
Brian Giunta
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2011
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-6-3

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