# Thiamine deficiency and alcohol-induced neurodegeneration

> **NIH VA I01** · VA MEDICAL CENTER - LEXINGTON, KY · 2020 · —

## Abstract

Alcohol abuse causes many long-lasting health consequences; one of which is impaired cognitive
functioning known as alcohol-associated dementia (AAD). AAD is caused by the morphological,
neurophysiological and biochemical changes in the brain. The most devastating feature of brain damage
following chronic alcohol abuse is neurodegeneration. Alcohol abuse is frequently associated with the
deficiency of thiamine (vitamin B1). Besides alcohol exposure, other factors, such as genetic background,
aging or nutritional status also contribute to thiamine deficiency (TD). The relationship between TD and
alcohol-induced neurodegeneration remains unclear. Our studies indicate that TD exacerbated alcohol-induced
neurodegeneration. Alcohol exposure caused significant endoplasmic reticulum ER stress in the brain. We
hypothesize that TD causes a deficiency in unfolded protein response (UPR) which function as a protective
response to alleviate ER stress-induced damage. MANF is an evolutionarily conserved neurotrophic factor and
an important UPR component. We further hypothesize that MANF is a key protein that maintains ER
homeostasis and TD-induced deficiency in MANF makes neurons more susceptible to alcohol-induced ER
stress and neurodegeneration. In this proposal, we will first investigate the effect of TD on MANF expression.
We will then determine the role of MANF in alcohol-induced ER stress and neurodegeneration. Finally, we will
determine whether manipulation of MANF expression in the brain can alter TD/alcohol-induced behavioral
deficits. As a unit, the proposal will investigate the mechanisms of how TD exacerbates alcohol-induced
neurodegeneration and establish a protective role of MANF in alcohol-induced neurodegeneration. It will not
only provide a novel insight into the interaction between TD and alcohol exposure in the context of AAD but
also identify potential therapeutic targets for the treatment of AAD.

## Key facts

- **NIH application ID:** 9832131
- **Project number:** 5I01BX001721-06
- **Recipient organization:** VA MEDICAL CENTER - LEXINGTON, KY
- **Principal Investigator:** JIA LUO
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-10-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832131

## Citation

> US National Institutes of Health, RePORTER application 9832131, Thiamine deficiency and alcohol-induced neurodegeneration (5I01BX001721-06). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9832131. Licensed CC0.

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