# BLRD Research Career Scientist Award Application

> **NIH VA IK6** · VA NEW JERSEY HEALTH CARE SYSTEM · 2024 · —

## Abstract

Traumatic brain injury and other neurodegenerative disorders, e.g., Alzheimer’s Disease (AD),
amyotrophic lateral sclerosis (Lou Gehrig’s disease, ALS), and related conditions, have an especially
significant and increasing prevalence in the Veteran population. Gulf War illness has a high
incidence among Veterans that served in the 1990-1991 Persian Gulf conflict and neurologic
problems are common. It is essential that the underlying mechanisms that contribute to these
conditions are understood so that treatments can be developed to improve the outcomes for Veterans
and others. I have been studying the molecular genetic aspects of neurons and glia in the brain and
spinal cord to determine how we can best modulate regulatory pathways to block and reverse
neurodegenerative signaling that results in behavioral problems. In the course of these
investigations, we examine human CNS samples obtained from brain banks, animal models, and
model neurons in tissue culture. We evaluate gene expression changes and interactions that occur
during the course of neurodegeneration in a variety of brain and spinal cord samples and model
systems to compare alterations that are specific to the various disorders so that we can characterize
factors that can be targeted to obtain neuroprotection and improved functional performance. I have
determined key mechanisms responsible for central nervous system neurodegeneration. Areas of
current discovery include Alzheimer's disease, important to the aging Veteran and general population,
and traumatic brain injury which is becoming increasingly understood in terms of injury exposures in
sports and importantly, is unfortunately the signature affliction of recently deployed military forces. In
this arena I have, for example, identified therapeutic targets by defining neurodegenerative
mechanisms and demonstrating that attacking these targets results in reduced activation of caspase-
3, improved neuroprotective gene expression in the brain, and reduced functional deficits, measured
with behavioral and cognitive tests, by treatment after injury. We have found that several genes
responsible for the loss of neuronal function are influenced significantly by a handful of inflammatory
responsive regulatory factors that control the transcription rates, or gene expression, of the proteins
important to neuronal health. For example, we found that inflammatory responsive regulatory
transcription factors can be modulated to produce neuroprotective levels of intracellular proteins
through selective upregulation and downregulation. By treating models with our intracellular,
regulatory modulators, we have not only positively influenced biochemical pathways, we have
demonstrated improved memory function in neurodegenerative conditions compared to untreated
controls. We are currently extending this research to additional neurological problems that occur
more frequently in Veterans and are seeking to advance beneficial therapeutic strategies.

## Key facts

- **NIH application ID:** 10720895
- **Project number:** 5IK6BX006188-02
- **Recipient organization:** VA NEW JERSEY HEALTH CARE SYSTEM
- **Principal Investigator:** Bruce A. Citron
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-10-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10720895

## Citation

> US National Institutes of Health, RePORTER application 10720895, BLRD Research Career Scientist Award Application (5IK6BX006188-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10720895. Licensed CC0.

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