Molecular mechanism of neuropathogenesis and current therapeutics for neuroAIDS
Human immunodeficiency virus (HIV) penetrates into the brain at initial phase of infection. Transmigration of HIV into the brain can be explained as “Trojan Horse” mechanism where infected CD4 T cells, monocytes and macrophages cross the blood brain barrier via cell independent manner. HIV infection to the brain may result in neuroAIDS with several neurological complications like dementia, mylopathy and neuropathy. Key barriers for the effective drug delivery to the brain are the complex structure of brain barriers which limit the transmigration of drugs, weak pharmacokinetic profile and bio-distribution of antiretroviral drugs. In addition, conventional therapeutics available for the treatment of HIV have a potential to reduce the mortality and morbidity in infected individuals by decreasing the plasma viral load and modulating the immune system but still there is a great need to develop the novel strategies for the effective drug entry to the CNS. In this article the role of viral proteins (Tat, Nef) in neuropathogeneis, crucial transporter systems (GLUT-1 glucose carrier and efflux transporters like P-glycoprotein) for limited drug delivery and current approaches for the treatment of neuroAIDS have been emphasized. Furthermore, the future perspectives talks about on the recent advancement in the novel drug delivery systems and strategies for the treatment and cure of neuroAIDS.