Saving Dopamine Neurons to Prevent 'Parkinsonbyeong'

Revealing the Role of Protein Modification in Dopamine Neuron Survival Control
Inhibition of Dopamine Neuron Death and Motor Function Recovery via O-GlcNAcylation Activation

Elderly couple. Photo by Getty Images Bank

[Asia Economy Reporter Hwang Junho] A new clue has been discovered for treating Parkinson's disease, a degenerative brain disorder in which muscle paralysis or spasms cause slowed movement. Through animal experiments, researchers succeeded in improving Parkinson's symptoms by inhibiting protein modifications involved in the death of dopamine neurons. The research team evaluated this as a contribution to developing new treatments for Parkinson's disease.

The research team led by Professor Kim Jae-ik of Ulsan National Institute of Science and Technology announced on the 12th that they proved through animal experiments that activating O-GlcNAcylation in dopamine neurons can alleviate Parkinson's disease-induced motor dysfunction to near normal levels. The related research results were recently published in the international journal 'Brain.'

'Inhibition of Phosphorylation by Glycation' A Clue to Prevent Early Dopamine Neuron Death

Changes When Increasing O-GlcNAcylation in Dopamine Neurons

Parkinson's disease is the second most prevalent degenerative brain disorder after Alzheimer's disease (dementia). When affected by this disease, dopamine neurons in the brain die, reducing dopamine secretion. If the cause of dopamine neuron death is identified and blocked, Parkinson's disease can be treated. Currently, the method used is supplementing dopamine precursors to prevent motor dysfunction, but this research aims to develop a more fundamental treatment.

The research team discovered a clue to alleviate motor dysfunction in Parkinson's disease. They found that O-GlcNAcylation, a type of post-translational modification (PTM) of intracellular proteins, can be involved in the function and death of dopamine neurons.

Considering that sugar groups and phosphate groups competitively bind to the same sites on protein amino acid chains, that O-GlcNAcylation is most active in the brain, that phosphorylation is a normal PTM but excessive phosphorylation has recently been identified as a strong cause of neuron death, the team concluded that O-GlcNAcylation can inhibit phosphorylation and prevent early dopamine neuron death.

Increased Glycation Alleviated Motor Dysfunction Symptoms

The Impact of O-GlcNAcylation on the Survival and Function of Dopamine Neurons and the Pathology of Parkinson's Disease

The research team demonstrated this through animal experiments. When Parkinson's disease model mice were administered a drug that inhibits O-GlcNAc degradation, early death of dopamine neurons was suppressed, and motor dysfunction symptoms were significantly alleviated.

Professor Kim Jae-ik explained, "O-GlcNAcylation has long been suspected to play an important role in neurons and the nervous system. Through this study, we revealed a new role of O-GlcNAcylation acting specifically on dopamine neurons among various types of neurons in the brain."

He added, "Recently, protein hyperphosphorylation has been identified as a cause of early neuron death in intractable degenerative brain diseases such as Alzheimer's and Parkinson's. This study is significant in showing the potential for fundamental treatment of degenerative brain diseases by inhibiting hyperphosphorylation through O-GlcNAcylation."

This content was produced with the assistance of AI translation services.