# HIV promotes dendritic degeneration by altering microtubule-associated protein

> **NIH NIH R21** · GEORGETOWN UNIVERSITY · 2022 · $429,000

## Abstract

Abstract
Despite antiretroviral therapy (ART), HIV can cause cognitive and mental health disorders, referred to as HIV-
associated neurocognitive disorders (HAND). HAND pathology, which is characterized by synaptodendritic
damage, resembles that observed in aging brain. At present, there are no effective treatments for HAND. In
addition, it has been suggested that anti-retroviral therapy (ART) impairs neuronal function; thus, the
identification of new mechanisms that can lead to a reduction of HIV-mediated neuropathology is important.
The major goal of this project is to discover the biological mechanisms whereby HIV reduces dendrites. Our
preliminary data show that the cerebrospinal fluid (CSF) and postmortem brains of people living with HIV
(PLWH), whose neurocognitive performance is reduced, have a higher content of microtubule-associated
protein 2 (MAP2), when compared to cognitively normal PLWH. MAP2, which is highly enriched in dendrites,
binds to microtubules (MTs) and plays a key role in their formation and elongation, and helps neuronal
trafficking. However, MAP2 has different isoforms that, when accumulate in neurons, they promote impairment
of MTs function and dendritic degeneration. HIV could directly alter MAP2 levels or use viral proteins to impair
the function of MTs. Because the HIV-mediated loss of dendrites is experimentally reproducible by the
envelope glycoprotein gp120, we hypothesize that HIV affects the overall function of dendritic MTs by a gp120-
dependent mechanism which encompasses an alteration of MAP2 binding to MTs. Two Specific Aims are
proposed to test this hypothesis. In Aim 1, we will examine the mechanisms whereby HIV/gp120 alters MAP2.
In Aim 2, we will use various approaches to reduce or enhance MAP2 isoforms and examine their role in
dendritic injury. A better understanding of these mechanisms is instrumental for drug development to reduce
the incidence of HAND.

## Key facts

- **NIH application ID:** 10618573
- **Project number:** 1R21NS131097-01
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Italo Mocchetti
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2022-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10618573

## Citation

> US National Institutes of Health, RePORTER application 10618573, HIV promotes dendritic degeneration by altering microtubule-associated protein (1R21NS131097-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10618573. Licensed CC0.

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