# Tailor-Made Molecular Chaperones to Target Protein Misfolding

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2023 · $541,441

## Abstract

Project Summary
Numerous aging-associated neurodegenerative diseases are rooted in the misfolding of
proteins and the generation of toxic protein aggregates, with Alzheimer's disease (AD)
being the most prevalent form of dementia characterized by the aggregation of the
amyloid beta peptide (Aβ) and hyperphosphorylated tau. Few effective strategies are
currently available for most of these diseases. In this proposal, we will test the
hypothesis that novel molecular chaperones can be evolved to recognize and target
aggregation-prone proteins and ameliorate their associated toxicity, thus providing a new
approach to intervene in protein misfolding diseases. Using Aβ as the model substrate,
our specific goal is to provide proof-of-principle for a new platform for the directed
evolution of molecular chaperones that can protect Aβ sequences from aggregation. The
efficacy of the evolved chaperones in ameliorating Aβ toxicity will be tested in vitro and
in vivo. The proposed studies will establish a new, facile, and broadly applicable
approach to evolve novel molecular chaperones tailored to specific aggregation-prone
target proteins and thus broadly impact diverse diseases rooted in protein misfolding.
The evolved TMMCs are expected to achieve a specificity that is normally unattainable
by other approaches, such as small molecules or general chaperone upregulation, and
can supplement the reduced capacity of the cellular chaperone network during aging to
protect neuronal cells from toxic protein aggregates.

## Key facts

- **NIH application ID:** 10717818
- **Project number:** 1R01AG082969-01
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Shu-ou Shan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $541,441
- **Award type:** 1
- **Project period:** 2023-08-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10717818

## Citation

> US National Institutes of Health, RePORTER application 10717818, Tailor-Made Molecular Chaperones to Target Protein Misfolding (1R01AG082969-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10717818. Licensed CC0.

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