ABSTRACT
Compromised structure and function of the blood-brain barrier (BBB) is one of the pathological hallmarks of brain infection by HIV-1. BBB damage during HIV-1 infection has been associated with modified expression of tight junction (TJ) proteins, including occludin. Recent evidence indicated occludin as a redox-sensitive, multifunctional protein that can act as both an NADH oxidase and influence cellular metabolism through AMPK kinase. One of the newly identified functions of occludin is its involvement in regulating HIV-1 infection. Studies suggest that occludin expression levels and the rate of HIV-1 infection share a reverse, bidirectional relationship; however, the mechanisms of this relationship are unclear. In this review, we describe the pathways involved in the regulation of HIV-1 infection by occludin. We propose that occludin may serve as a potential therapeutic target to control HIV-1 infection and to improve the lives of people living with HIV-1.
Subject(s)
HIV Infections , HIV-1 , Humans , Occludin/metabolism , HIV-1/metabolism , Brain/metabolism , Blood-Brain Barrier/metabolism , Tight Junction Proteins/metabolism , Tight Junctions/metabolismABSTRACT
HIV-associated comorbidities, such as ischemic stroke, are prevalent in people with HIV (PWH). Several studies both in animal models and humans have revealed an association between activation of the inflammasome in HIV-1 infection and stroke. The gut microbiota is an important component in controlling neuroinflammation in the CNS. It has also been proposed to be involved in the pathobiology of HIV-1 infection, and has been associated with an increase in activation of the inflammasome. In this review, we provide an overview of the microbiota-gut-inflammasome-brain axis, focusing on the NLRP3 inflammasome and dysregulation of the microbiome as risk factors that may contribute to the outcome of ischemic stroke and recovery in PWH. We also focus on the potential of targeting the NLRP3 inflammasome as a novel therapeutic approach for PWH who are at risk of developing cerebrovascular diseases.
Subject(s)
HIV Infections , HIV-1 , Ischemic Stroke , Stroke , Animals , Humans , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Ischemic Stroke/complications , Dysbiosis/complications , Stroke/complications , HIV Infections/complicationsABSTRACT
Se establecieron las bases teórico-metodológicas de un modelo curricular con orientación hacia el desarrollo temprano y creciente de habilidades profesionales, en correspondencia con las exigencias actuales para el desempeño en cualquiera de los niveles de atención del Sistema Nacional de Salud y de la sociedad cubana contemporánea, con un enfoque de desarrollo integral de la personalidad profesional, congruente con los valores socialmente establecidos en nuestro país.
