HIV-1 and amyloid beta peptide interactions at the blood-brain barrier level

• Autorzy: Toborek M. , Andras I.
• Języki publikacji: EN

Abstrakty

EN

An increase in the older population infected with HIV-1 is an emerging development in HIV-1 epidemiology. Aging is connected with increased deposition of amyloid beta peptide (amyloid beta) in the brain. In the current study, we propose that amyloid beta and HIV-1 can potentiate their toxic effects at the blood–brain barrier (BBB) level. To address this notion, we employed an in vitro model of human brain microvascular endothelial cells (HBMEC) directly exposed to HIV-1 or co-cultured with HIV-1 infected human monocytes. Exposure of HBMEC to amyloid beta (1-40) in the presence of HIV-1 resulted in a markedly increased amyloid beta binding/entry into HBMEC. We then hypothesized that HIV-1 may either increase binding/entry of externally added amyloid beta or elevate the amount of endogenously produced amyloid beta. The receptor for advanced glycation end products (RAGE) is known to be involved in the transport of amyloid beta across the BBB into the brain. RAGE immunoreactivity was stronger and RAGE protein levels were elevated in HBMEC exposed to HIV-1 as compared to control. In contrast, exposure to HIV-1 decreased expression of lipoprotein receptor related protein-1 (LRP1) which is the main receptor that transports amyloid beta from the brain to blood. These results indicate that HIV-1 can decrease the ability of the BBB to transport amyloid beta from the brain and thus predispose the brain to increased amyloid beta accumulation. Supported by MH072567, MH63022, and NS39254

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.285-286

Twórcy

autor

Toborek M.

• Molecular Neuroscience and Viscular Biology Laboratory, Department of Neurosurgery, University of Kentucky, Lexington, KY, USA

autor

Andras I.

• Molecular Neuroscience and Viscular Biology Laboratory, Department of Neurosurgery, University of Kentucky, Lexington, KY, USA