# Role of Local Protein Synthesis in CNS Axon Regeneration

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $346,719

## Abstract

Project Summary
We will use the unique advantages of the lamprey nervous system to determine whether after spinal cord injury
(SCI), local protein synthesis in the axon tip plays a role in the mechanism of axon regeneration. It has long
been assumed that axon regeneration depends on protein synthesis in the cell body, the proteins then being
transported to the growing axon tips. However, based mainly on observations in tissue culture and injured
peripheral nerve, where ribosomes and mRNAs have been detected in axons, a role has been proposed for
local protein synthesis in axon regeneration. Locally synthesized proteins might be used to form new axon
constituents, or be transported retrogradely to the cell body to signal cell survival and growth-associated gene
expression. Until now, evidence for local protein synthesis in the central nervous system (CNS) has been
limited primarily to growth cones in early stages of neuronal development in vivo and in vitro. In mature
mammalian CNS, where axons do not regenerate, the capacity for local translation is maintained primarily in
the dendritic tree; the axons have minimal capacity to synthesize proteins. However, work in lamprey spinal
cord, where axons do regenerate, suggests that mature CNS axons regenerate without growth cones, i.e., their
tips lack filopodia, have relatively little F-actin, are packed with neurofilaments (NFs), and elongate much more
slowly than developing axons. This raises the question whether local protein synthesis plays a role in
regeneration of mature CNS axons, even though they do not have growth cones. We previously showed that
after SCI in lamprey, mRNA and ribosomes accumulate in the axon tips, and that actively growing tips have
more mRNA than static or retracting tips. Moreover, the mRNAs include abundant neurofilament transcripts,
but much less actin transcripts, the opposite of findings in mammalian axons growing in vitro or in injured
peripheral nerve. Now we will use RNAseq to analyze laser microdissected cytoplasm from large, identified
reticulospinal neurons, and micro-aspirated axoplasm from their injured axon tips, to identify mRNAs
associated with axon regeneration. We will determine how the mRNAs are regulated in the cell body and get to
the tip by determining a) the role of the MAP kinase pathway in signaling axotomy and triggering regeneration,
and b) the time course of mRNA appearance along the axon and in the growing tip. Then we will determine
whether we can enhance regeneration by locally overexpressing some proteins with micro-injected mRNAs,
and whether we can inhibit regeneration by a) inhibiting local protein synthesis with locally applied protein
synthesis inhibitors, and b) locally applying morpholino antisense oligonucleotides. This study will help us
determine where and how to target therapies to enhance axon regeneration and restore function after SCI.

## Key facts

- **NIH application ID:** 10146489
- **Project number:** 5R01NS097846-05
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** MICHAEL EDGAR SELZER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,719
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146489

## Citation

> US National Institutes of Health, RePORTER application 10146489, Role of Local Protein Synthesis in CNS Axon Regeneration (5R01NS097846-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10146489. Licensed CC0.

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