# Role of FABP7 in ALS models

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $382,090

## Abstract

Abstract
 The goal of this proposal is to establish whether decreasing fatty acid-binding protein 7 (FABP7)
expression ameliorates motor neuron degeneration in amyotrophic lateral sclerosis (ALS) models. The FABPs
belong to a family of small (~15kDa) and widely expressed intracellular proteins. All FABPs exhibit high affinity
reversible binding of saturated and unsaturated long-chain fatty acids as well as other lipids. FABPs have been
considered biologically silent chaperones of fatty acids, but it has now become clear that the FABPs are central
regulators of lipid metabolism, energy homeostasis and inflammation. FABPs participate in fatty acid
metabolism regulating their uptake and transport but can also regulate signaling processes by distributing
and/or sequestering ligands for nuclear receptors such as peroxisome proliferator activated receptors
(PPARs). FABP7 (also known as brain lipid binding protein, BLBP) is expressed in neural stem cells
throughout development and its expression decreases and becomes restricted to astrocytes and radial-like
glial cells in the adult central nervous system. Reactive astrocytes up-regulate FABP7 expression in multiple
pathological conditions. To effectively transport and donate bound ligands, FABPs display affinities in the same
range or slightly weaker than those exhibited by PPARs. However, up-regulation of FABPs expression can
create a “sink effect”, negatively regulating the availability of endogenous ligands for PPARs (i.e., increased
intracellular levels of FABPs will result in decreased PPARs activation). PPARs govern the expression of
genes involved in coordinating metabolic and inflammatory pathways in the cell. Thus, decreased PPAR
activity can contribute to altered lipid-mediated signaling and NF-kB activation, two prominent features of ALS-
astrocytes. Our data show for the first time that FABP7 up-regulation may be responsible for the decreased
PPAR activity and concomitant increase in NF-kB activity in ALS-astrocytes. Using cell culture and mouse
models we will evaluate the hypothesis that decreasing FABP7 expression should restore normal activity of
these two interconnected networks and can potentially provide protection against astrocyte-mediated motor
neuron death in ALS models.

## Key facts

- **NIH application ID:** 10415000
- **Project number:** 5R01NS122973-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Marcelo R Vargas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,090
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10415000

## Citation

> US National Institutes of Health, RePORTER application 10415000, Role of FABP7 in ALS models (5R01NS122973-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10415000. Licensed CC0.

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