Flipping the switches: CD40 and CD45 modulation of microglial activation states in HIV associated dementia (HAD)
Year: 2011
Type: article
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.
Source: Molecular Neurodegeneration
Authors: Jon Salemi, Demian F Obregon, Anthony Cobb, Spenser Reed, Edin Sadic, Jingji Jin, Francisco Fernandez, Jun Tan, Brian Giunta
Institution: University of South Florida
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,090
Awards: Oral administration of TeaMemTM inhibits Alzheimer's disease pathogenesis, The impact of HAART on HIV-1 Tat induced brain aging, DiosMemTM, a natural gamma-secretase inhibitor, opposes AD pathogenesis, HUCBC modulation of Alzheimer-like pathology and behavioral changes, The Role of HIV-1 Tat in Alzheimer's Disease
OpenAlex ID: W2121836546