# Modulation of autophagic flux as a therapeutic strategy for Alzheimer's disease

> **NIH NIH RF1** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $1,773,833

## Abstract

Autophagy is a catabolic cellular recycling process that maintains cellular homeostasis and its dysregulation has
been implicated in numerous diseases, including neurodegenerative diseases such as Alzheimer’s disease (AD).
AD is an age-related neurodegenerative disease that affects more than 5 million people in the United States.
Autophagic and lysosomal defects have been observed in AD, including accumulation of autophagic vesicles
and lysosomal intermediates as well as defective lysosomal processing of autophagosome contents. Small-
molecule autophagy activators that could overcome these defects could potentially halt disease progression
through the restoration of cellular homeostasis and the prevention of neuronal cell damage. Our central
hypothesis is that small-molecule autophagy activators will restore autophagic and lysosomal homeostasis and
exhibit neuroprotective effects that will prevent disease progression and ameliorate Alzheimer’s disease
symptoms in vivo. This hypothesis will be tested through the overall objectives of this proposal to optimize an
autophagy activator as an in vivo tool compound and drug lead and to evaluate the efficacy of autophagy
modulation for the resolution of AD phenotypes in disease-relevant assays and in vitro neuronal models as well
as an in vivo model. Our approach is innovative because we have identified mTOR-independent autophagy
activators and will identify and validate their unique targets and mechanisms of action in neuronal models to
potentially reveal new targets for AD drug discovery. The aims of this proposal will contribute to the achievement
of our long-term goal to develop new therapeutics for unmet needs in neurodegenerative diseases. FDA-
approved drugs for AD treat the symptoms of the disease but do not improve the underlying cell damage that
leads to disease progression, further highlighting the need for novel neuroprotective therapeutic options.

## Key facts

- **NIH application ID:** 10417514
- **Project number:** 1RF1AG076653-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Swetha Gowrishankar
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,773,833
- **Award type:** 1
- **Project period:** 2022-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10417514

## Citation

> US National Institutes of Health, RePORTER application 10417514, Modulation of autophagic flux as a therapeutic strategy for Alzheimer's disease (1RF1AG076653-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10417514. Licensed CC0.

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