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GM1-Oligosaccharide Rescues Rotenone-Impaired Neuronal Polarization Through RhoA/ROCK Modulation and Mitochondrial
Pablo E A Rodríguez1, Guillermo N Colmano2, Andrea Pellegrini3
1Secretaría de Ciencia y Tecnología, Ministerio de Producción, Ciencia e Innovación Tecnológica, Gobierno de la Provincia de Córdoba, Córdoba, Argentina.
Journal of Neurochemistry
|July 1, 2026
Summary
The ganglioside osGM1 protects and restores neuronal development damaged by neurotoxins like rotenone. It targets cytoskeletal and mitochondrial issues, showing therapeutic potential for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Neuronal polarization is crucial for neural circuit formation.
- Neurotoxins disrupt neuronal development by affecting cytoskeletal dynamics and mitochondrial function.
- Gangliosides like GM1 may offer neuroprotection.
Purpose of the Study:
- To investigate the neuroprotective and neurorestorative effects of GM1 and its derivative osGM1.
- To evaluate their efficacy against rotenone-induced neurotoxicity in primary hippocampal neurons.
- To elucidate the underlying mechanisms involving cytoskeletal and mitochondrial regulation.
Main Methods:
- Primary hippocampal pyramidal neurons from E18 rat embryos were cultured.
- Neurons were exposed to the mitochondrial neurotoxin rotenone.
- The effects of GM1 and osGM1 on neuronal polarity, axonal growth, and mitochondrial function were assessed.
- RhoA/ROCK pathway activation and actin dynamics were analyzed.
Main Results:
- Rotenone impaired neuronal development, axonal growth, and mitochondrial integrity.
- Both GM1 and osGM1 promoted recovery of neuronal polarity and axonal growth.
- osGM1 demonstrated superior efficacy, even reversing actin stabilization-induced deficits.
- osGM1 normalized RhoA/ROCK hyperactivation and partially restored mitochondrial function.
Conclusions:
- osGM1 exhibits significant neuroprotective and neurorestorative properties against rotenone toxicity.
- osGM1 acts as a multi-target modulator of cytoskeletal and mitochondrial dysfunction.
- osGM1 holds translational potential as a therapeutic agent for neurotoxin-induced neuronal damage.
