# Identification of factors essential for age-related neuronal health:  insights into common mechanisms of neurodegeneration

> **NIH NIH R21** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $429,000

## Abstract

In a genetic screen conducted in adult zebrafish to select mutations that disrupt age-related neuronal
homeostasis, 36 genes were identified. Many of these loci have previously been shown as associated or
causative to human neurodegenerations such as Alzheimer's, Huntington's, Parkinson's and Spinocerebellar
Ataxia diseases. This proposal describes experiments to address cellular functions of a subset of the genes
identified from this screen with unknown mechanisms of action. First, complete loss of function mutations will
be generated in this subset though engineered large genomic deletions within coding sequence. Next, these
will be analyzed for their impact on neuronal homeostasis by monitoring several cellular stress responsive
pathways known to be activated during neurodegeneration including the ER stress/Unfolded Protein
Response, Oxidative Stress Response, and Autophagy/Mitophagy. In anticipation of these studies, our group
has established imaging-based reporters for each of these processes. In addition, mutants will also be
evaluated in the context of several sensitized genetic strains in which these stress-responsive pathways have
been compromised. Finally, the autonomy of mutant impact will be investigated through cell-type specific gene
disruption in multiple neuronal and non-neuronal cell types. These studies will provide important base-line
information and rationale for carrying out next-step analysis in mammalian, including human, homologues that
may represent critical targets for therapeutic intervention to promote neuronal health and prevent
neurodegeneration.

## Key facts

- **NIH application ID:** 10057170
- **Project number:** 1R21AG066038-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Brian A Link
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057170

## Citation

> US National Institutes of Health, RePORTER application 10057170, Identification of factors essential for age-related neuronal health:  insights into common mechanisms of neurodegeneration (1R21AG066038-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10057170. Licensed CC0.

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