# Folding, Misfolding and Oligomerization of TDP-43

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2020 · $45,520

## Abstract

Project Summary
Folding, Misfolding and Oligomerization of TDP-43
 Life expectancy has been significantly extended through innovation in modern medicine.
Ironically, with longevity comes the greater threat of neurodegenerative diseases: chronic,
debilitating illnesses with no cures and limited treatments. The World Health Organization has
projected neurodegenerative diseases to overtake cancer in the number of annual disease-
related deaths by 2040, second only to cardiovascular disease.
 TDP-43 is a 43 kDa RNA splicing regulator, as well as one of the best biomarkers for
several neurodegenerative diseases including Alzheimer’s disease (AD) and amyotrophic lateral
sclerosis (ALS). TDP-43 aggregates have been found in 97% of ALS patients and up to 50% of
AD patients. The molecular mechanisms of TDP-43 aggregate formation is not well understood;
TDP-43 contains an N-terminal oligomerization domain and an intrinsically disordered C-
terminal region, both of which are believed to contribute in TDP-43 pathological aggregation.
The N-terminal domain has been shown to oligomerize and contribute to TDP-43 self-assembly.
This self-assembly is a part of TDP-43 native function in stress granule formation. However,
there is speculation that the self-assembly of TDP-43 can lead to aggregation; thus, studying
the parameters of N-terminal oligomerization may offer insight into aggregation pathways.
 TDP-43 is a member of a class of proteins known as intrinsically disordered proteins due to
its disordered C-terminal domain. This domain is the site of known mutations and post-
translational modifications observed in the brains of patients of neurodegenerative diseases.
Cleaved C-terminal domain fragments are also found in patients’ brains.
 In the proposed project, TDP-43 N-terminal and C-terminal domains will be studied using
single-molecule and ensemble biophysics techniques to characterize their functions and identify
structural switches that are responsible for TDP-43 aggregation.

## Key facts

- **NIH application ID:** 9989195
- **Project number:** 5F31NS103380-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Phoebe Sisoen Tsoi
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989195

## Citation

> US National Institutes of Health, RePORTER application 9989195, Folding, Misfolding and Oligomerization of TDP-43 (5F31NS103380-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9989195. Licensed CC0.

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