Modulatory Effects of Nicotine on neuroHIV/neuroAIDS

Nicotine, one of the key active ingredients in tobacco smoke, exerts its effects via binding to nicotinic acetylcholine receptors (nAChRs). Although both negative and positive pharmacological effects of nicotine have been shown in numerous animals and human studies, its interaction with human immunodeficiency virus-1 (HIV-1) have not been fully elucidated. Even though combined anti-retroviral therapy (cART) limits the progression of HIV-1 to acquired immune deficiency syndrome (AIDS), HIV-associated neurocognitive disorders (HAND) remain prevalent. There is thus a compelling need to enhance our understanding of HAND-related neurologic dysfunction. Some biochemical pathways and physiological dysfunctions have been found to be shared by HAND and Alzheimer's (AD) or Parkinson's (PD) diseases, and nicotine may exert the same neuroprotection in HAND that has been observed in both AD and PD. In the past dozen years, various potential therapeutic effects of nicotine such as neuroprotection have been revealed in both in vivo and in vitro studies, including using HIV-1 transgenic (HIV-1Tg) rat model, which mimics HIV-infected patients receiving cART. In the current review, we describe recent progress in the prevalence of HIV/AIDS with and without cigarette smoking, some animal models for studying neural dysfunction associated with HIV-1 infection, elucidating the modulatory effects of cigarette smoking/nicotine on HIV/AIDS, the anti-inflammatory effects of nicotine, and the neuroprotective effects observed in HIV-1Tg rat model. Taken together, these findings suggest the following: although tobacco smoking does cause deleterious effects in both health and disease conditions such as HIV infection, nicotine, the significant component of tobacco smoke, has been shown to possess some neuroprotective effects in HIV patients, possible via its anti-inflammatory activities. It is therefore necessary to study nicotine's dual effects on neuroHIV/neuroAIDS in hope of better defining the potential medical uses of nicotine or its analogues, and to make them available in a purer and less dangerous form.