DkIT Study Reveals New Knowledge About Proteins That Could Aid Treatment & Prevention of Tremors in Parkinson’s Disease

16 January 2020

New insights into the role of the novel accessory protein, LINGO1 typically found in the brains of people with neurodegenerative disorders associated with tremors could support the quest for better treatments for patients.

An international research team led by Dundalk Institute of Technology (DkIT) has made a breakthrough discovery which identifies a new subunit of large conductance potassium (BK) ion channels that has major implications for understanding disorders of the nervous system associated with tremor, such a Parkinson’s Disease and Essential Tremor.

The study forms part of the cross-border research project BREATH (Borders and Regions Airways Training Hub) which is funded by the EU’s INTERREG VA Programme, managed by the Special EU programmes body (SEUPB) and DkIT Research Office.

The EU-INTERREG VA funded study which included collaboration with University of Edinburgh, Queen’s University of Belfast and Reno School of Medicine (USA) was published today in the leading scientific journal, ‘Proceedings of the National Academy of Science of the United States of America (PNAS)’. VIEW HERE

As Parkinson’s Disease advances, the symptoms such as tremors can become extremely debilitating and patients often require around-the-clock nursing care. Previous research has determined that the transmembrane protein called LINGO1 is found in cerebellar neurones that control movement, and is overexpressed in patients with Parkinson’s disease and essential tremor. Studies have proven that a loss of these BK channels in cerebellar neurones also results in tremor and movement disorders.

Key findings within this study include:

  • LINGO1 assembles with BK channels in human brain. 
  • LINGO1 modifies the activity of BK channels through two mechanisms: i) by decreasing the number of channels in the cell membrane and ii) reducing the activity of BK channels already in the membrane. 
  • Thus, LINGO1 is a novel regulator of BK channels that reduces BK channel activity and may contribute to the tremor associated with elevated LINGO1 expression. 

Speaking today, Professor Mark Hollywood, Project Lead for this Study and Principal Investigator at the Smooth Muscle Research Centre (SMRC) at DkIT said,

“These findings will have a significant impact on the understanding of the causes of tremor in Movement Disorders such as Parkinson’s and they suggest a new target for the development of innovative therapeutics and strategies that could dramatically improve the lives of people living with these debilitating disorders in the future.”

This study was initiated in the SMRC at DkIT in December 2018 and used a combination of single cell electrophysiology, protein biochemistry and molecular modelling to elucidate that LINGO1 is a regulatory subunit that functionally ‘knocks down” BK channels in the cell membrane.

Prof Mike Shipston, Dean of Biomedical Sciences and Professor of Physiology at University of Edinburgh, also collaborated in the study and commented: 

“By bringing together an international team with complementary skills this multi-disciplinary study promises to reveal how therapeutic targeting of LINGO1 and BK channels in the future may help reduce the motor disorders associated with major disorders of the human brain.”

Dr Tim McCormac, Head of Research & Graduate Studies at DkIT added,

“We are immensely proud to be part of this ground-breaking discovery and I would like to congratulate the entire SMRC team who led the study and our international research partners for their work in bringing this study to fruition. DkIT’s lead role in the project is a testament to the outstanding research capability of the Institute, both in blue skies and translational research. This work further underlines the strategic importance of SMRC and the Health research agenda at DkIT.”

Commenting on the study Gina McIntyre, CEO of the Special EU Programmes Body, which manages the INTERREG VA Programme, said:

The EU’s INTERREG VA Programme has invested significantly in the health and life sciences sector in order to support cross-border research work like this which has tremendous potential to positively impact the lives of many citizens. It is part of a project with partners based across Northern Ireland, Ireland and Western Scotland who by working together have been able to pool their knowledge, experience and expertise to shape an extremely important development in future healthcare. This is a truly inspirational discovery and I am delighted that the study is complete and has now been published.”

Widespread impact

Parkinson’s Disease is classified as a Movement Disorder, affecting approximately 12,000 people in Ireland[1] - a figure that is predicted to double over the next 20 years[2]. There are 3 main symptoms to Parkinson’s Disease - tremor (shaking), slowness of movement and rigidity (muscle stiffness) but there are many other symptoms too. The Global Burden of Disease study[3] estimates that 6.2 million individuals currently have Parkinson’s disease and currently, there is no cure.

  • This study arose from a project in the BREATH programme, which was focused on examining the role of novel regulatory ion channel subunits in airways epithelium and smooth muscle. A recent genome wide array study (Hansel et al., 2015 Genome wide association study identification of novel loci associated with airway responsiveness in COPD, Am J Respir Cell Mol Biol 53 (2) 226-234) has demonstrated that a related protein LINGO-2, may be a marker for altered airway responsiveness in COPD. 
  • In picture (l-r): Gina McIntyre, CEO of the Special EU Programmes Body; Dr Lorcan McGarvey, Principal Investigator at QUB; Prof. Keith Thornbury, Principal Investigator at SMRC, DkIT; Prof. Mark Hollywood, Principal Investigator at SMRC, DkIT; Prof. Lorraine Martin, Principal Investigator at QUB; Prof. Gerard Sergeant, Principal Investigator at SMRC, DkIT)

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