# Genetic control mechanisms of long-term neuronal survival

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2024 · $633,810

## Abstract

PROJECT SUMMARY
The proposed research aims to unravel fundamental mechanisms behind neuronal survival across an
organism's lifespan, shedding light on specialized RNA regulation pivotal for prolonged neuronal resilience.
Essential for learning, memory, and environmental adaptation, mature neurons must persist throughout an
organism's life, yet our understanding of the intricate genetic regulations enabling this endurance remains
incomplete. Prior studies predominantly emphasized competition for external cues and growth factors in
establishing neural circuits and preventing cell death. Our research uncovers intrinsic genetic mechanisms
facilitating continuous neuronal survival. Notably, during differentiation, neurons alter their apoptosis regulation,
becoming more resistant to cell death triggers. This transformation coincides with global reprogramming of
apoptosis-related genes at both transcriptional and post-transcriptional levels, resulting in the generation of
neural-specific alternative isoforms. A significant focus lies on understanding the role of specific gene elements
which exhibit crucial regulatory functions. We have determined a dozen of these splicing controls with
implicated functions in controlling neuronal survival and cell death. Our preliminary data show that splicing
alternation significantly impairs neuronal health. We propose three independent and interrelated overarching
aims for systematic exploration of these elements in influencing neuronal apoptosis. Additionally, by
investigating the impact of exon deletions and genetic manipulations, we seek to determine their continuous
necessity for long-term neuronal survival. Our interdisciplinary team, adept in genetics, neurobiology,
molecular cellular biochemistry, and computational biology, uniquely positions us to tackle these critical
questions. Through innovative methodologies and rigorous investigations, we endeavor to unveil neuron-
specific regulatory mechanisms governing apoptosis competence. Such discoveries may not only reshape our
comprehension of intrinsic neuronal survival strategies but also pave the way for novel strategies to enhance
neuronal resilience and combat neurological disorders affecting brain tissue equilibrium and circuitry formation.

## Key facts

- **NIH application ID:** 10998540
- **Project number:** 1R01NS139485-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Sika Zheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $633,810
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998540

## Citation

> US National Institutes of Health, RePORTER application 10998540, Genetic control mechanisms of long-term neuronal survival (1R01NS139485-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10998540. Licensed CC0.

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