# Animal models of small heat shock proteins interactions with Tau

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2021 · $308,203

## Abstract

Project Summary
Alzheimer's disease is a terminal neurodegenerative disease that is characterized by multiple
neuropathological hallmarks and the diagnostic accumulation of intracellular neurofibrillary
tangles (NFTs) and extracellular amyloid plagues. NFTs arise form the aggregation of
phosphorylated Tau and have been observed in familial mutants thereof. Other forms of
neurodegeneration associated with tauopathy include frontotemporal dementia and chronic
traumatic encephalopathy. The main line of defense against protein aggregation in the cell is the
chaperone function of a group of heat shock proteins. The ATP-independent small heat shock
proteins (sHSPs) are tasked by the rapid and efficient buffering of aggregation-prone protein.
Despite evidence of involvement of sHSPs in many neurogenerative diseases including AD, a
mechanistic understanding of the interaction between sHSP and aggregation-prone Tau is
lacking. This supplement request will expand our efforts on the parent grant, EY12018, which is
focused on deciphering the physiological roles of HspB1, HspB4 and HspB5, to include the
interactions of these sHSPs with aggregation-prone Tau. The research plan will bring to bear an
integrated perspective emphasizing zebrafish genetics, fluorescence imaging and biochemical
analysis of binding by sHSPs which has proven successful in elucidating molecular events
associated with another aging-related protein aggregation disease, lens cataracts. It will take
advantage of the simplicity of terminally differentiated lens fiber cells to characterize the
interaction of tau with sHSPs in a living animal. The research plan will investigate the effects of
changes in chaperone capacity of sHSPs as well as oxidative stress on the aggregation of tau.
Together, the data will address an unexplored aspect of neurodegeneration in the unique model
of the zebrafish lens. The results will provide potential therapeutic strategies to interfere with
tauopathies.

## Key facts

- **NIH application ID:** 10293700
- **Project number:** 3R01EY012018-24S1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Hassane S Mchaourab
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $308,203
- **Award type:** 3
- **Project period:** 1998-02-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10293700

## Citation

> US National Institutes of Health, RePORTER application 10293700, Animal models of small heat shock proteins interactions with Tau (3R01EY012018-24S1). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10293700. Licensed CC0.

---

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