Scientists from Nanyang Technological University, Singapore (NTU Singapore) and the Korea Advanced Institute of Science & Technology (KAIST) have identified a new mechanism that causes the hallmark symptoms of Parkinson’s disease, namely tremors, rigidity, and loss of voluntary movement.
Their discovery gives a new perspective on three decades of conventional wisdom in Parkinson’s disease research. It also opens up potential new avenues of treatment that could help alleviate the motor problems experienced by patients of the disease, which are estimated at more than 10 million worldwide. The research was published in scientific journal 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 which is jointly set up by NTU Singapore and Imperial College London. 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.
Parkinson’s disease is caused by a lack of dopamine, a chemical in the brain that transmits neural signals but it is unknown how the disease leads to its characteristic motor problems.
Smooth, voluntary movements, such as reaching for a cup of coffee, are controlled by a part of the brain called the basal ganglia. It issues instructions that either trigger or suppress actions; and movement depends on a proper balance between the two sets of instructions.
A low level of dopamine causes the basal ganglia to more severely suppress the instructions. Scientists have long assumed that this suppression leads to the motor problems in Parkinson’s disease.
However, when the research team tested this assumption using a new light-based experimental technique in mice, they found that if suppression instructions from the basal ganglia were more strongly triggered, the motor controlling part of the brain actually became hyperactive. This hyperactivity led to abnormal muscular stiffness and tremor very similar to the symptoms of Parkinson’s disease. The key is a neural phenomenon that kicks in after such strong suppression, known as ‘rebound firing’.
Conversely, when rebound firing was itself blocked in mice that were genetically engineered to be dopamine deficient, they showed normal movement without Parkinson’s disease symptoms, proving the key role of ‘rebound firing’.
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.
Ang Hui Min
Corporate Communications Office
Nanyang Technological University
KAIST Public Relations Office
About Nanyang Technological University, Singapore
A research-intensive public university, Nanyang Technological University, Singapore (NTU Singapore) has 33,500 undergraduate and postgraduate students in the colleges of Engineering, Business, Science, Humanities, Arts, & Social Sciences, and its Interdisciplinary Graduate School. It also has a medical school, the Lee Kong Chian School of Medicine, set up jointly with Imperial College London.
NTU is also home to world-class autonomous institutes – the National Institute of Education, S Rajaratnam School of International Studies, Earth Observatory of Singapore, and Singapore Centre for Environmental Life Sciences Engineering – and various leading research centres such as the Nanyang Environment & Water Research Institute (NEWRI), Energy Research Institute @ NTU (ERI@N) and the Institute on Asian Consumer Insight (ACI).
Ranked 11th in the world, NTU has also been ranked the world’s top young university for the last four years running. The University’s main campus has been named one of the Top 15 Most Beautiful in the World. NTU also has a campus in Novena, Singapore’s medical district.
For more information, visit www.ntu.edu.sg
KAIST is the first and top science and technology university in Korea. KAIST was established in 1971 by the Korean government to educate elite scientists and engineers committed to industrialization and economic growth in Korea. Since then, KAIST has been the gateway to advanced science and technology, innovation, and entrepreneurship.
KAIST has now emerged as the most innovative global institution with more than 11,000 students enrolled in five colleges and six schools. KAIST continues to strive for making the world better through the pursuit of excellence in education, convergence research, and globalization.
For more information, visit http://www.kaist.ac.kr