# Cell Non-Autonomous Regulation of NeuronalProteostasis

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $47,916

## Abstract

Project Summary
 The capacity to response to internal and external stressors is critical for cellular survival
throughout life and during aging. Despite the presence of protective mechanisms, cellular damage
accrues over an organism’s lifetime, including accumulated damage to the proteome. Such deficits to
protein homeostasis have a particularly deleterious effect in neurons, where they contribute to the
development and progression of age-associated neurodegenerative diseases, such as Alzheimer’s
disease. Cell-intrinsic mechanisms for responding to proteotoxicity have been identified; three major
stress responses (the cytoplasmic heat shock response, the endoplasmic reticulum unfolded protein
response, and the mitochondrial unfolded protein response) act cell autonomously in neurons and
other cell types to ameliorate proteotoxic stress. There is also mounting evidence that neuronal health
in this context is modulated by communication from non-neuronal tissues; however, very little is
known about the relevant underlying mechanisms.
 The major objective of the proposed work is to characterize the nature of cell non-autonomous
regulation of neuronal proteostasis, using C. elegans as a model. First, we will determine how
perturbing stress response pathways in non-neuronal tissues affect neuronal proteostasis. Recent
work has shown that activation of each of the three proteostatic stress responses in neurons cell non-
autonomously protects peripheral tissues from proteotoxicity; we hypothesize that non-autonomous
protection might also occur in the reverse direction, i.e. that activation of these stress responses in
non-neuronal tissues can promote neuronal proteostasis, which we will test by in Aim 1. Second, we
will more broadly explore mechanisms of periphery-to-neuron communication that alter neuronal
proteostasis. We will identify genes that function cell non-autonomously to regulate neuronal
proteostasis using a tissue-specific knockdown screening approach in Aim 2. Together these aims
are likely to yield insight into the mechanisms by which inter-tissue communication influences
neuronal health and could lead to the identification of new therapeutic targets for diseases associated
with neuronal proteotoxic stress.
 The sponsor for the proposed work, Dr. Andrew Dillin, is a renowned expert in proteostasis
with an excellent training record; his laboratory at UC Berkeley represents an ideal environment for
the applicant to develop the research, mentorship, and communication skills necessary to become an
independent investigator.

## Key facts

- **NIH application ID:** 10359732
- **Project number:** 5F32AG065381-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Corinne Pender
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $47,916
- **Award type:** 5
- **Project period:** 2020-02-14 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359732

## Citation

> US National Institutes of Health, RePORTER application 10359732, Cell Non-Autonomous Regulation of NeuronalProteostasis (5F32AG065381-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10359732. Licensed CC0.

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