# Enhanced Skeletal Muscle Proteostasis as a Modulator of Alzheimer's Disease

> **NIH NIH R03** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $148,500

## Abstract

PROJECT SUMMARY
Alterations in protein quality control (also known as proteostasis) are a key feature of Alzheimer’s disease brains,
and autophagy, a lysosomal-mediated degradation pathway, is significantly impacted in AD. Importantly, while
the importance of autophagy to health and disease is well documented, how this process is regulated in a whole
organism context remains poorly understood. Individual organs in the body, particularly skeletal muscle, seem
to play a pivotal role in regulating proteostasis and autophagy in other tissues; including the CNS. This project
investigates the role of skeletal muscle Transcription factor E-B (TFEB), a master regulator of autophagy and
cellular clearance, in regulating CNS proteostasis during Alzheimer's disease. We will perform cutting-edge
parabiosis paradigms and transcriptome analyses to dissect this muscle-to-brain axis in mouse models of
enhanced skeletal muscle proteostasis, Alzheimer's disease and tau proteotoxicity. In collaboration with the
University of Kansas Alzheimer's Disease Center, we will also examine proteostasis function in skeletal muscle
samples from AD patients, with the goal of identifying novel peripheral biomarkers for AD. These studies will
address muscle-to-brain cell-nonautonomous proteostasis signaling and uncover novel pathways promoting
neuroprotection in the context of Alzheimer's disease, which will be crucial for therapy development for
neurodegenerative disorders associated with dysfunctional proteostasis.

## Key facts

- **NIH application ID:** 10145316
- **Project number:** 7R03AG063215-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Constanza Javiera Cortes
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $148,500
- **Award type:** 7
- **Project period:** 2019-04-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145316

## Citation

> US National Institutes of Health, RePORTER application 10145316, Enhanced Skeletal Muscle Proteostasis as a Modulator of Alzheimer's Disease (7R03AG063215-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10145316. Licensed CC0.

---

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