A joint research team has discovered that if the function of a causative gene protein – Heat Shock Protein Family A Member 9 (HSPA9) – declines through mutation, it can significantly reduce peroxisome and cause Parkinson’s disease.
The researchers presented the importance of peroxisome in the area of Parkinson’s disease, where mitochondrial dysfunction has been considered to be the major cause. They also expected organelle regulators would be used as new targets in developing treatments for the disease.
The peroxisome is a monolayer organelle present in most eukaryotic cells and plays a vital role in the energy metabolism of the brain, liver, heart, and lung tissue. Genetic problems in generation and decomposition of peroxisome can lead to congenital abnormalities of the central nervous system such as Zellweger Syndrome (ZS).
As the studies found the cause of peroxisome dysfunction due to congenital genetic mutations and aging, researches on the recovery of damaged peroxisome drew attention as a new therapeutic strategy in the neurodegenerative diseases field, such as Zellweger Syndrome and Parkinson’s disease, the research team said.
The joint team was composed of Professor Cho Dong-hyung of the Life Science Department at Kyungpook National University, Lee Kyu-sun, head of Bionano Center at Korea Research Institute of Bioscience & Biotechnology, and Wonkwang University College of Medicine.
The three organizations conducted the study with the support of the state institutes, and the research was published in a scientific journal Autophagy on Friday, with the title of "Loss of HSPA9 induces peroxisomal degradation by increasing pexophagy."
According to the study, the mutation of HSPA9, a protein in encoded mitochondria, could increase oxidative stress and decrease peroxisome in cell organelles, and develop Parkinson’s disease through aggravating neurons or muscle cells.
The study also found that peroxisome reduction occurs through the regulation of peroxisome-specific autophagy called the pexophagy, a cellular quality control mechanism.
The joint team discovered that the pexophagy decomposes toxic protein aggregates that cause Alzheimer's dementia, and identified the collapse of mitochondrial calcium homeostasis as a common cause of neurodegenerative diseases such as Alzheimer's and Parkinson's disease.
The study implies that the function of cell organelles and mitochondria should be actively studied in neurodegenerative diseases, cancer, and metabolic diseases.
"This research revealed the importance of controlling the maintenance of peroxisome function to treat neurodegenerative diseases effectively," Professor Cho said.
Lee, the Bionano Center head, also said, "Development of a new drug that targets both peroxisome function regulator and interaction of cell organelles such as peroxisome and mitochondria can be widely used in other developments such as cancer, metabolic diseases, age-related diseases."
The following are some questions and answers concerning the result of this research.
Question: What is the difference between achievements in this study from those of previous studies?
Answer: This study is the first to find the relationship between the functions of peroxisome and Parkinson’s disease. It differs from previous studies in that it revealed mitochondria dysfunction or toxic aggregate protein, such as alpha-synuclein, for the first time.
Q: Where can the study result be used?
A: The result can be widely applied to the development of a new treatment strategy for Parkinson’s disease by restoring the function of peroxisome. Plus, treating age-related diseases such as cancer, metabolic, and musculoskeletal disorders where peroxisome energy metabolism and antioxidant control capacity matters.
Q: How long would it take for commercialization?
A: Discovering ingredient candidates for treatment, conducting clinical trials, and how fast the trial progress will determine the time required for commercialization.
This research is a base study that presents new confirmed concepts and suggests treatment targets using cell strain and an animal model.
Q: What tasks need to be done for commercialization?
A: Presenting a new treatment target and establishing a treatment development strategy for recovering HSPA9 and peroxisome function is the top priority based on the analysis of peroxisomal dynamics found in this study and the peroxisomal regulatory function of genes to Parkinson’s disease.
Q: Why have you chosen to conduct this research?
A: The team has been working on mitochondrial and pexophagy in neurodegenerative diseases such as Alzheimer's and Parkinson’s disease, and found that HSPA9 gene has a possibility of peroxisomal regulation. We began a collaborative study on peroxisome function in Parkinson’s disease by sharing the role of mammalian cell strain and the drosophila disease model.
Q: Do you have a specific goal to achieve?
A: Peroxisome, which plays a significant role in regulating intracellular energy metabolism and oxidation stress, has been relatively less studied than mitochondria. However, as the importance of peroxisome in various disease surges, we want to deliver a new treatment strategy and approach for cancer, metabolic disorders, and neurodegenerative diseases with an in-depth study on peroxisomal function.
Q: Any words to the upcoming researchers?
A: This study is an outcome of a random meeting between researchers at a conference. It is possible to draw a significant achievement through a joint research team with various fields and opportunities.
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