# Mechanisms of corticospinal tract regeneration

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $328,682

## Abstract

This project is dedicated to discovering ways to induce regeneration of the corticospinal tract
(CST and recovery of motor function after spinal cord injury (SCI). The CST is the pathway that
is responsible for the ability to move voluntarily. Damage to the CST as a result of a spinal cord
injury is the reason people are paralyzed. The project is based on discoveries that the CST can
be induced to regenerate following spinal cord injury by targeting molecular pathways that
control cell growth in development, specifically phosphatase and tensin homolog (PTEN). PTEN
is responsible for shutting down the type of protein synthesis that is critical for cell growth during
development. PTEN acts by blocking the mammalian target of Rapamycin, (mTOR), so deletion
of PTEN releases inhibition on mTOR, which in turn allows the cell to synthesize proteins that
are critical for cell growth. We have shown that genetic deletion of PTEN in mice and
knockdown of PTEN in rats with AAVshRNA allows CST neurons to mount a robust
regenerative response, which is accompanied by recovery of motor function. The new project is
based on exciting and novel recent discoveries that targeting PTEN in adult nerve cells induces
a state of youthful vigor in which there is perpetual growth in addition to an ability to regenerate
after injury. The overall goal of the project is to determine the cellular and molecular
mechanisms of this growth-enabled state and identify the genes that are turned on or shut off
during growth and regeneration. Defining the pattern of gene expression that underlies the
growth-enabled state in nerve cells will identify targets for future therapeutic interventions to
promote regeneration and repair after injury and potentially protect nerve cells from
degeneration in neurodegenerative disorders.

## Key facts

- **NIH application ID:** 9895871
- **Project number:** 5R01NS108189-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** OSWALD STEWARD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $328,682
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895871

## Citation

> US National Institutes of Health, RePORTER application 9895871, Mechanisms of corticospinal tract regeneration (5R01NS108189-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9895871. Licensed CC0.

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