# K channel, NLRP3 inflammasome and Meth exacerbation of HAND

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $411,544

## Abstract

Abstract
Despite effective combination antiretroviral therapy (cART), virus persists in brain at low levels often in a latent
or restricted manner. Immune activation and inflammation continues and is linked to viral and cellular
neurotoxic proteins and co-morbid infections along with drugs of abuse. The severity of inflammation that
occurs during cART is well known to be worsened by methamphetamine (Meth). The mechanisms that underlie
such disease outcomes remain poorly understood. Complicating the ability to decipher mechanisms is that
antiretroviral drugs (ARVs) may themselves affect inflammatory responses and elicit neurotoxicity during long-
term usage. Thus, HIV, drugs of abuse and ARVs are believed to orchestrate changes in the brain’s
microenvironment leading to microglia (MG) activation and consequent inflammatory activities. These, over
time, affect the development of HIV-associated neurocognitive disorders (HAND). To date, there is
considerable interest in strategies that regulate MG activation and resultant inflammation. Thus, investigations
on development of specific biomarkers to judge the severity of inflammation and identification of specific
targets to control MG activation and inflammation are of immediate importance. MG express outward delayed
rectifier Kv1.3, with a direct tie into functional marker of MG activation and NLRP3 inflammasome is involved in
HIV-induced MG activation. However, there is very limited information available on how Kv1.3 can be “best”
utilized as a biomarker for Meth potentiation of HIV-associated MG NLRP3 inflammasome activation. To this
end, we seek funds to develop Kv1.3 as a potential biomarker and to evaluate its potential as an intersecting
target for HIV, Meth and ARVs in laboratory and animal models. In specific aim 1, we will determine and
characterize the role of Kv1.3 in Meth- and ARV-induced potentiation of MG activation, migration, production of
neurotoxins and neurotoxic activity via NLRP3 activation. In specific aim 2, we will investigate the relationships
between Kv1.3-associated MG NLRP3 activation and HIV-associated neuronal injury and behavioral deficits in
infected humanized mice. We theorize that Kv1.3 channels can be harnessed as physiological biomarkers for
inflammation and neurotoxicity seen during HAND. This rests in the fact that such channels closely regulate
MG activation, migration and production of pro-inflammatory substances. Overall, these studies, if successful,
may have the potential to develop a biomarker for judging the severity of HIV-, Meth- and ARV-associated
neuroinflammation and to identify a potential intersecting target for the development of therapeutic strategies.

## Key facts

- **NIH application ID:** 10197086
- **Project number:** 5R01DA050540-03
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** HUANGUI Hank XIONG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $411,544
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197086

## Citation

> US National Institutes of Health, RePORTER application 10197086, K channel, NLRP3 inflammasome and Meth exacerbation of HAND (5R01DA050540-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10197086. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*