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Updated: Aug 8, 2025

Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration

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Published on: March 17, 2014

Deneddylating enzyme SENP8 regulates neuronal development.

Jae-Man Song^1,2,3, Minji Kang^1,2,3, Seungha Lee^1,2,3

¹Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.

Journal of Neurochemistry

|February 27, 2023

Summary

This summary is machine-generated.

SENP8, a deneddylating enzyme, regulates neuronal development by impacting neurite outgrowth and synapse maturation. Its developmental expression suggests a role in neurodevelopmental disorders.

Keywords:

SUMO Peptidase Family Member, NEDD8 Specific metabotropic glutamate receptor 7 neurite outgrowth neurodevelopmental disorders postsynaptic density protein 95 synapse maturation

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Area of Science:

Neuroscience
Cell Biology
Biochemistry

Background:

Neddylation, a post-translational modification, is crucial for synaptic function and neuronal development.
The role of deneddylating enzymes in neuronal development remains largely unexplored.
We hypothesized that deneddylating enzymes counteract neddylation to regulate neuronal development.

Purpose of the Study:

To investigate the role of deneddylating enzymes in neuronal development.
To identify key deneddylating enzymes involved in regulating neurite outgrowth and synaptic maturation.
To explore the therapeutic potential of targeting deneddylation in neurodevelopmental disorders.

Main Methods:

Primary rat cultured neurons were used to study deneddylation.
SENP8 expression levels were analyzed during different developmental stages.
Neurite outgrowth, actin dynamics, Wnt/β-catenin signaling, and autophagy were assessed.
Excitatory synapse maturation was evaluated in response to SENP8 manipulation.

Main Results:

SENP8 was identified as a key neuronal deneddylase targeting global neuronal substrates.
SENP8 expression is developmentally regulated, peaking early postnatally.
SENP8 negatively regulates neurite outgrowth via actin dynamics, Wnt/β-catenin signaling, and autophagy.
SENP8 manipulation impairs excitatory synapse maturation.

Conclusions:

SENP8 plays a critical role in regulating neuronal development.
SENP8 negatively impacts neurite outgrowth and excitatory synapse maturation.
SENP8 is a potential therapeutic target for neurodevelopmental disorders.