Healthy Ageing by Tackling Neurodegeneration

The World Health Organisation (WHO) defines healthy ageing as “the process of developing and maintaining the functional ability that enables wellbeing in older age.” How to achieve this, is one of the major challenges to address when populations around the world are ageing at an ever-faster pace.

For example, the fastest growing neurological condition in the world, for which there is no cure, is Parkinson's disease. Researchers at the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU) at the University, which studies cell signaling, are making significant advances in understanding the cellular mechanisms underlying neurodegenerative diseases.

Much of the research undertaken by Professor Dario Alessi over his last 15 years has focused on understanding how mutations in a protein called LRRK2 can lead to higher susceptibility to Parkinson’s. His team have made seminal advances, including the discovery that LRRK2 deactivates targets called Rab proteins, providing more understanding of the cascade of events that can lead to Parkinson’s or that might be manipulated to alleviate symptoms. His work has revolutionised the scientific tools available worldwide to study the mechanisms of Parkinson’s disease and has directly stimulated new drug development programmes by the pharmaceutical industry. Together with Dr Esther Sammler, Clinical Group Leader in the MRC PPU and Honorary Consultant Neurologist at NHS Tayside, he has developed biomarkers for the LRRK2 signalling pathway that are critical to evaluating the effectiveness of new therapeutics in clinical trials.

Significant advances in Parkinson’s research have also been focussed on the protein PTEN-induced kinase 1 or PINK1.  Studies by Professor Miratul Muqit contributed to the discovery of loss of function PINK1 mutations in hereditary early-onset Parkinson’s patients. PINK1 activity causes the protein Parkin to bind to mitochondria and target them for destruction. In 2017, in collaboration with the van Aalten lab, Muqit’s group solved the first crystal structure of PINK1 that revealed how disease mutations abolish its activity. Collectively, this work directly stimulated interest amongst industry to develop drugs that activate PINK1 and Parkin.

People affected by Parkinson’s are a critical part of the research process for the MRC-PPU. The Dundee Parkinson’s Research Interest Group (DRIG) was formed in 2017 by Parkinson’s UK and regularly interacts with researchers in Dundee. Members of DRIG are kept informed on the research progress, and can input into and participate in the research. This interaction benefits both researchers and people with Parkinson’s:

The quest to develop new therapies and treatments continues for researchers in Dundee. Last year, Professors Alessi and Muqit, with colleagues at Stanford, received a multi-million-dollar grant from the Aligning Science Across Parkinson’s (ASAP) initiative and joined its international network of researchers to generate new knowledge in Parkinson’s disease. ASAP aims to accelerate the pace of discovery and inform the path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. Parkinson’s research in Dundee has also been supported by other funders including the Medical Research Council, Wellcome, The Michael J Fox Foundation, and Parkinson’s UK and through the Division of Signal Transduction Therapy, a unique collaboration involving the MRC-PPU, other leading researchers in Dundee’s School of Life Sciences, and several the world’s leading pharmaceutical companies.