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Unlocking the Keys to Parkinson's Disease
A KAIST research team has identified a new mechanism that causes the hallmark symptoms of Parkinson’s disease, namely tremors, rigidity, and loss of voluntary movement.
The discovery, made in collaboration with Nanyang Technological University in Singapore, presents a new perspective to three decades of conventional wisdom in Parkinson’s disease research. It also opens up new avenues that can help alleviate the motor problems suffered by patients of the disease, which reportedly number more than 10 million worldwide. The research was published in Neuron on August 30.
The research team was led by Professor Daesoo Kim from the Department of Biological Sciences at KAIST and Professor George Augustine from the Lee Kong Chian School of Medicine at NTU. Dr. Jeongjin Kim, a former postdoctoral fellow at KAIST who now works at the Korea Institute of Science and Technology (KIST), is the lead author.
It is known that Parkinson’s disease is caused by a lack of dopamine, a chemical in the brain that transmits neural signals. However, it remains unknown how the disease causes the motor
Smooth, voluntary movements, such as reaching for a cup of coffee, are controlled by the basal ganglia, which issue instructions via neurons (nerve cells that process and transmit information in the brain) in the thalamus to the cortex. These instructions come in two types: one that triggers a response (excitatory signals) and the other that suppresses a response (inhibitory signals). Proper balance between the two controls movement.
A low level of dopamine causes the basal ganglia to severely inhibit target neurons in the thalamus, called an inhibition. Scientists have long assumed that this stronger inhibition causes the motor problems of Parkinson’s disease patients.
To test this assumption, the research team used optogenetic technology in an animal model to study the effects of this increased inhibition of the thalamus and ultimately movement. Optogenetics is the use of light to control the activity of specific types of neurons within the brain.
They found that when signals from the basal ganglia are more strongly activated by light, the target neurons in the thalamus paradoxically became hyperactive. Called rebound excitation, this hyperactivity produced abnormal muscular stiffness and tremor. Such motor problems are very similar to the symptoms of Parkinson’s disease patients. When this hyperactivity of thalamic neurons is suppressed by light, mice show normal movments without Parkinson’s disease symptoms. Reducing the levels of activity back to normal caused the motor symptoms to stop, proving that the hyperactivity caused the motor problems experienced by Parkinson’s disease patients.
Professor Kim at KAIST said, “This study overturns three decades of consensus on the provenance of Parkinsonian symptoms.” The lead author, Dr Jeongjin Kim said, “The therapeutic implications of this study for the treatment of Parkinsonian symptoms are profound. It may soon become possible to remedy movement disorders without using L-DOPA, a pre-cursor to dopamine.”
Professor Augustine at NTU added, “Our findings are a breakthrough, both for understanding how the brain normally controls the movement of our body and how this control goes awry during Parkinson’s disease and related dopamine-deficiency disorders.”
The study took five years to complete, and includes researchers from the Department of Bio & Brain Engineering at KAIST.
The research team will move forward by investigating how hyperactivity in neurons in the thalamus leads to abnormal movement, as well as developing therapeutic strategies for the disease by targeting this neural mechanism.
Figure abstract: Inhibitory inputs from the basal ganglia inhibit thalamic neurons (upper). In low-dopamine states, like PD, rebound firing follows inhibition and causes movement disorders (middle). The inhibition of rebound firing alleviates PD-like symptoms in a mouse model of PD.
2017.09.22 View 9479 -
2010 International Presidential Forum was held successfully.
On October 11th, the 2010 International Presidential Forum on “The Role of the Research University in an S&T Dominated Era: Expectation & Delivery” was held successfully at the Westin Chosun Hotel in Seoul. The third International Presidential Forum to be held, participants of the 2010 Presidential Forum engaged in an in-depth discussion about the direction that research universities should take in the 21st Century.
On its opening, President Nam Pyo Suh delivered a congratulatory message saying, “This forum is a meaningful gathering where research universities will suggest role models and find ways research universities can contribute to the progress of mankind in this century.”
Following, Lee Ki Jun, CEO of the Korean Federation of Science and Technology Societies said, “The common goal of the world’s research universities is to solve the problems mankind is facing together. I believe that the discussion we will hold today at the forum will point to the future direction of research universities.”
“To produce next generation engineers meeting global standards, exchange and dual degree programs between universities must be strengthened,” said Lars Pallesen, President of the Technical University of Denmark. “Research universities must support the exchange between students beyond cultural and national borders to adapt to the global market.”
Ichiro Okura, Vice President of Tokyo Institute of Technology, presented on the “Asian Science and Technology Pioneering Institutes of Research and Education, ASPIRE.” ASPIRE is a community created by the coalition between science and technology universities in the Far East. Its purpose is to contribute to sustainable global growth by educating high-quality human resources and lead Asia’s technology innovation based on science and technology development.
“For research universities to solve today’s global issues, universities must create new ideas by performing fundamental studies and developing innovative technology. The financial resources of universities must be focused with choices based on results,” remarked President Suh.
Zaini Ujang, Vice-President of the Universiti Teknologi Malaysia stated that “the Malaysian government is planning on converting from a ‘labor-intensive economy’ to an ‘innovative leading economy’ with the goal of joining the advanced countries by 2020. In today’s science and technology era where innovative technology is necessary, research universities have an important role of developing the knowledge environmental system to lead the world economy.” Vice-President Ujang then explained what strategies Malaysian research universities devised in the innovative leading economy era to create research universities that bring creativity and innovation.
Tod A. Laursen, President of KUSTAR, said that “KUSTAR has a leading role in bringing science and technology and manpower necessary in converting the oil-centered economy of UAE to a knowledge-based economy. KUSTAR will continuously strengthen international cooperation to become not only the best engineering university in the Arab region but in the world.”
At this year’s forum, thirty international presidents and vice presidents from 24 universities in 15 countries including Georgia Tech, Technical University of Denmark, Technion-Israel Institute of Technology, University of Queensland, Tokyo University, Nanyang Technological University, University Teknologi Malaysia and Hong Kong Institute of Science and Technology along with forty national figures such as the presidents of Hanyang University and Handong Global University, governmental bureaucrats and representatives from national business and institutions participated.
2010.10.20 View 14826