Research Report by Sarah Chowdhury, C'22
Abstract
HIV-associated neurocognitive disorders (HAND) are a spectrum of disorders characterized by neurocognitive impairments such as memory loss. Previous scholarly works have observed altered amyloid processing and the presence of amyloid-beta plaques in the brains of HAND patients, which is characteristic of neurodegenerative diseases such as Alzheimer’s disease. However, it is not yet known whether there is a mechanistic relationship
between the upstream pathways of amyloid processing in HAND. This review will examine excitotoxicity in HIV/HAND and other neurodegenerative diseases, as well as the mechanisms involved in altered amyloid processing. In particular, this review will elucidate the upstream pathways involved in amyloid processing in HIV-associated excitotoxicity and their interactions with the amyloidogenic (BACE1) and non amyloidogenic (ADAM10) pathways. Finally, this review will describe potential interactions that have yet to be defined in the context of HAND and the brain that may provide insight into the specific mechanisms involved in HIV-induced excitotoxicity and amyloid processing.
This review will examine excitotoxicity in HIV/HAND and other neurodegenerative diseases, as well as the mechanisms involved in altered amyloid processing.
The full research report can be found below:
Figure 1. Mechanism of HIV-associated excitotoxicity in the brain This figure depicts the upstream mechanism of excitotoxicity in HAND. As HIV-infected monocytes cross the blood-brain barrier and mature into macrophages, they infect and activate microglia. Macrophage secretions, including inflammatory molecules, HIV proteins, and excitatory neurotransmitters, subsequently impact neurons and mediate increased calcium influx via the NMDA receptor. This results in excitotoxicity that has further implications for oxidative stress and amyloidogenic processing in HAND. Figure created with BioRender.com.