Potential neuroprotective role of astroglial exosomes against smoking-induced oxidative stress and HIV-1 replication in the central nervous system

ABSTRACT

Introduction: HIV-1-infected smokers are at risk of oxidative damage to neuronal cells in the central nervous system by both HIV-1 and cigarette smoke. Since neurons have a weak antioxidant defense system, they mostly depend on glial cells, particularly astrocytes, for protection against oxidative damage and neurotoxicity. Astrocytes augment the neuronal antioxidant system by supplying cysteine-containing products for glutathione synthesis, antioxidant enzymes such as SOD and catalase, glucose for antioxidant regeneration via the pentose-phosphate pathway, and by recycling of ascorbic acid.

Areas covered: The transport of antioxidants and energy substrates from astrocytes to neurons could possibly occur via extracellular nanovesicles called exosomes. This review highlights the neuroprotective potential of exosomes derived from astrocytes against smoking-induced oxidative stress, HIV-1 replication, and subsequent neurotoxicity observed in HIV-1-positive smokers.

Expert opinion: During stress conditions, the antioxidants released from astrocytes either via extracellular fluid or exosomes to neurons may not be sufficient to provide neuroprotection. Therefore, we put forward a novel strategy to combat oxidative stress in the central nervous system, using synthetically developed exosomes loaded with antioxidants such as glutathione and the anti-aging protein Klotho.

KEYWORDS:

• Neurons
• astrocytes
• oxidative stress
• smoking
• HIV-1
• exosomes
• neuroprotection
• therapeutic target

Article highlights

• Cigarette smoke induces oxidative stress and subsequently promotes HIV-1 replication and NeuroAIDS in the CNS.

• As neurons have a weak antioxidant defense mechanism, they depend on astrocytes for neuroprotection against oxidative stress.

• Astrocytes support the neuronal antioxidant system by supplying energy substrates, antioxidant enzymes, and antioxidant molecules.

• Antioxidants are possibly carried to the neurons via extracellular vesicles called exosomes.

• Synthetically-developed exosomes loaded with antioxidants such as catalase, glutathione, and the anti-aging protein Klotho could be an efficient strategy for offsetting smoking-induced oxidative stress and HIV-1 replication in the CNS.

This box summarizes key points contained in the article.

Declaration of interest

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the National Institute of Health grants DA042374 and AA022063.