# Protection against Alzheimer's Disease proteins by novel ubiquitin processes

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2021 · $236,472

## Abstract

ABSTRACT
Alzheimer's Disease (AD) is highly prevalent, incurable and will continue to grow in impact and reach
as our population's age increases. In AD, Aβ and Tau proteins convert from normal protein folding into
toxic amyloid conformations. These processes cause neuronal dysfunction and, ultimately, death.
Ground-breaking work has been conducted to understand how and why proteins such as Aβ and Tau
become toxic and cause neurodegeneration. Still, the etiology of AD remains unclear and solutions
for it in the clinic presently elude us.
Our laboratory has a long-standing interest in diseases of the nervous system caused by proteins
harboring abnormally elongated polyglutamine repeats. Among these diseases is Spinocerebellar
Ataxia Type 3 (SCA3), the focus of the currently funded grant, R01 NS086778. In recent work with the
causative protein in SCA3 we found that unique processes that involve the small modifier protein,
ubiquitin, have suppressive effects.
Ubiquitin is best known for its role in targeting proteins for degradation by the proteasome. But, this
small protein has many other functions in the cell. Ubiquitination leads to various substrates and mod-
ifications, among which are poly-ubiquitin chains that are not attached onto another protein, referred
to as unanchored or free chains. We have found that unanchored chains suppress toxicity from polyg-
lutamine species, such as the SCA3 protein. Through this application, we propose to extend these
observations by investigating the role of free ubiquitin chains in the cellular response against Aβ and
Tau in AD.

## Key facts

- **NIH application ID:** 10283294
- **Project number:** 3R01NS086778-08S1
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Sokol Todi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,472
- **Award type:** 3
- **Project period:** 2014-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283294

## Citation

> US National Institutes of Health, RePORTER application 10283294, Protection against Alzheimer's Disease proteins by novel ubiquitin processes (3R01NS086778-08S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10283294. Licensed CC0.

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