Soluble Insulin Receptor Levels in Plasma, Exosomes, and Urine and Its Association With HIV-Associated Neurocognitive Disorders.

Background: HIV-associated neurocognitive disorders (HAND) are one of the HIV-associated comorbidities affecting 20-50% of the people with HIV (PWH) infection. We found that the soluble insulin receptor (sIR) levels in plasma and cerebrospinal fluid (CSF) were significantly higher in HIV-infected women. The mechanism of sIR release into the plasma remains unknown, but the detection of the sIR in exosomes may uncover novel mechanisms of sIR secretion from HIV-infected cells and its contribution to HIV disease progression and HAND development.

HIV Infection Induces Extracellular Cathepsin B Uptake and Damage to Neurons.

HIV-associated neurocognitive disorders prevail in 20-50 percent of infected individuals. Macrophages transmigrate through the blood brain barrier during HIV-1 infection, triggering neuronal dysfunction. HIV-infected macrophages secrete cathepsin B (CATB), and serum amyloid p component (SAPC), inducing neuronal apoptosis by an unknown mechanism.

Microwave & magnetic proteomics of macrophages from patients with HIV-associated cognitive impairment.

Objective: HIV-infected monocytes can infiltrate the blood brain barrier as differentiated macrophages to the central nervous system, becoming the primary source of viral and cellular neurotoxins. The final outcome is HIV-associated cognitive impairment (HACI), which remain prevalent today, possibly due to the longer life-span of the patients treated with combined anti-retroviral therapy. Our main goal was to characterize the proteome of monocyte-derived macrophages (MDM) from HACI patients, and its association with their cognitive status, to find novel targets for therapy.

Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids.

The abuse of anabolic androgenic steroids (AAS) has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG) axis is one of the body systems that is mainly influenced by steroidal hormones.

Interacting partners of macrophage-secreted cathepsin B contribute to HIV-induced neuronal apoptosis.

Objective: HIV-1 infection of macrophages increases cathepsin B secretion and induces neuronal apoptosis, but the molecular mechanism remains unclear.

Design: We identified macrophage-secreted cathepsin B protein interactions extracellularly and their contribution to neuronal death in vitro.

Methods: Cathepsin B was immunoprecipitated from monocyte-derived macrophage supernatants after 12 days postinfection.

Macrophage derived cystatin B/cathepsin B in HIV replication and neuropathogenesis.

Mononuclear phagocytes including monocytes and macrophages, are important defense components of innate immunity, but can be detrimental in HIV-1 infection by serving as the principal reservoirs of virus in brain and triggering a strong immune response. These viral reservoirs represent a challenge to HIV-1 eradication since they continue producing virus in tissue despite antiretroviral therapy. HIV-1 associated neurocognitive disorders (HAND) involve alterations to the blood-brain barrier and migration of activated HIV-1 infected monocytes to the brain with subsequent induced immune activation response.

Dysregulation of macrophage-secreted cathepsin B contributes to HIV-1-linked neuronal apoptosis.

Chronic HIV infection leads to the development of cognitive impairments, designated as HIV-associated neurocognitive disorders (HAND). The secretion of soluble neurotoxic factors by HIV-infected macrophages plays a central role in the neuronal dysfunction and cell death associated with HAND. One potentially neurotoxic protein secreted by HIV-1 infected macrophages is cathepsin B.