title: Flipping the switches: CD40 and CD45 modulation of microglial activation states in HIV associated dementia (HAD).
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.
authors.affiliation: Department of Psychiatry and Neurosciences, Neuroimmunology Laboratory, University of South Florida, College of Medicine, Tampa, FL 33613, USA. bgiunta@health.usf.edu.
authors.forename: Jon
authors.initials: J
authors.lastname: Salemi
authors.forename: Demian F
authors.initials: DF
authors.lastname: Obregon
authors.forename: Anthony
authors.initials: A
authors.lastname: Cobb
authors.forename: Spenser
authors.initials: S
authors.lastname: Reed
authors.forename: Edin
authors.initials: E
authors.lastname: Sadic
authors.forename: Jingji
authors.initials: J
authors.lastname: Jin
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernandez
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.forename: Brian
authors.initials: B
authors.lastname: Giunta