Juntendo News

Jun. 07, Wed, 2017



Potential therapeutic target for Parkinson’s disease

(Tokyo, 7 June)Investigations by scientists in Japan illustrate how the loss of a key mitochondrial protein facilitates the progression of Parkinson’s disease.

There is much evidence to suggest that dysfunction within cellular components contributes to the development and progression of the neurodegenerative disorder, Parkinson’s disease. However, exactly how individual genes and proteins contribute to the degradation of this integral cellular structure is unclear.
Mitochondria are sub-units within cells that help control biochemical processes such as energy production. They have a double-membrane structure, the inner membrane of which forms multiple layers or ‘cristae’. Each crista structure must remain intact in order for the mitochondria to perform their tasks effectively.
Now, Hongrui Meng and Chikara Yamashita at Juntendo University Graduate School of Medicine in Tokyo, and co-workers across Japan, have shown how a mitochondrial protein called CHCHD2 plays a key role in maintaining cristae structure and mitochondria integrity.
Meng and Yamashita’s team generated CHCHD2 mutant fruit flies (Drosophila), and examined what happened when CHCHD2 protein expression was lost. They found that this loss resulted in abnormal matrix structures and impairments to oxygen respiration in mitochondria. This in turn led to neuron loss through oxidative stress, and also to motor dysfunction – such as loss of climbing ability – as the flies aged.
When the researchers introduced a wild-type form of human CHCHD2 and a metabolic regulator 4E-BP to the flies, the dysfunctions were reversed. Further investigations showed that CHCHD2 binds to a mitochondrial protein cytochrome c along with a cell death regulator MICS-1. This binding helps cells to function properly and ensure correct cell death signaling in both mammalian cells and Drosophila.
As the team states in their paper published in Nature Communications, their results shed light on the role of CHCHD2 mutations in Parkinson’s disease and offer “potential therapeutic targets in Parkinson’s caused by mitochondrial dysfunction.”

Juntendo University Research: Potential therapeutic target for Parkinson’s disease