# A transcription factor complex specifically induced in neurodegeneration

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $405,000

## Abstract

In Alzheimer’s disease, axons are frequently the first part of a neuron to be affected. Neurodegenerative stimuli
trigger local signaling pathways that cause the retrograde spread of disease. We have found that application of
beta-amyloid within minutes triggers the intra-axonal synthesis of proteins that form a unique transcription
factor complex. The formation and function of this complex is required for the induction of neurodegeneration in
response to the AD-related peptide oligomeric Aβ1-42. The appearance of this transcription factor complex in
human postmortem brain tissue is restricted to AD brains. Here, we propose that the presence of this
transcription factor complex in the central nervous system is a hallmark of age-related neurodegenerative
disorders, including Alzheimer’s disease.
With the experiments in this proposal we will investigate the relevance of the disease-specific transcription
factor complex for the various pathological manifestations of Alzheimer’s disease, and we will study which
genes are up- or downregulated by it. We will contrast these results from Alzheimer’s disease brain with
findings in Parkinson’s disease brain, to determine how signaling via the complex differs in distinct
neurodegenerative disorders. Using genetic and pharmacological approaches, we will investigate in mouse
models of Alzheimer’s disease, whether interference with the disease-specific transcription factor complex
slows down or prevents disease progression.
Together, the results from this research project will establish a novel mechanism by which neurons react to
oligomeric Aβ1-42. Our results will provide the rationale for targeting this signaling mechanism and test the
feasibility of such an approach.

## Key facts

- **NIH application ID:** 10449333
- **Project number:** 5R01NS109607-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Ulrich Hengst
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2018-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449333

## Citation

> US National Institutes of Health, RePORTER application 10449333, A transcription factor complex specifically induced in neurodegeneration (5R01NS109607-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10449333. Licensed CC0.

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