A few questions were posed to PI Prof Dr Donato (Dino) DiMonte to gain his views on his work in Parkinson research and PD-MitoQUANT, in general. Dino is a senior researcher and leads the Neurodegeneration and Neuroprotection in Parkinson’s Disease Group at the German Center for Neurodegenerative Diseases (DZNE).
Please describe your day to day work.
It is difficult to describe a “typical” day of work. Most of the time, our working schedule involves specific tasks that vary from day to day and often have specific deadlines. For example, there are deadlines to apply for research grants, to complete research reports, to submit and review manuscripts and to perform administrative and educational duties. There are also commitments that, albeit quite regular, may not be part of a “daily” routine. These include attendance at research seminars, conference calls with research collaborators and participation in scientific meetings organized “in house” or requiring shorter or longer trips. Preparation of scientific presentations is another important activity that requires carving of specific time from our daily routine. With these caveats in mind, my typical working day often starts with reviewing and answering e-mail messages and telephone calls. I also like to dedicate my earlier hours at work to writing tasks, since I find it easier to concentrate on scientific manuscripts, grants or reports with a relatively “fresh” mind. I usually schedule personal or group meetings with members of my research team in the afternoon. I truly enjoy analyzing data and discussing the progress of our experimental work and new research plans with them. These meetings also represent important opportunities to review educational targets and career development opportunities with my younger collaborators. Finally, later in the afternoon or in the early evening, I like to spend some time reading scientific papers to catch up with the latest “news” in science in general and with the most recent advancements in my research field.
What is your general perspective on Parkinson research?
I have been involved in Parkinson’s research for the past 30 years and, during this time, our understanding of the processes underlying disease development and progression has improved tremendously. These improvements make me quite an optimist about the possibility that new therapeutic strategies will be successfully tested and could benefit patients in the near future.
“My component of the project will specifically deal with the assessment of mitochondrial function during the development and progression of alpha-synuclein deposition and neurodegeneration in experimental models of Parkinson’s that are well established in my laboratory at the DZNE in Bonn. As a member of PD-MitoQUANT, I will greatly benefit from the expertise of other colleagues at other PD-MitoQUANT sites. At the same time, I will be happy to share knowledge, laboratory experience and state-of-the-art infrastructure of my scientific team and research organization with the other PD-MitoQUANT partners. I am looking forward to an exciting and productive scientific “ride”!”
What are the big questions or current challenges in the field?
During the years, a variety of hypotheses concerning mechanisms of disease development have become “popular” or have faded in popularity among the scientific community. A few specific hypotheses, however, have attracted a consistently high level of scientific interest. Two examples are the roles that mitochondrial dysfunction and neuroinflammatory processes may have in neuronal injury in Parkinson. Mitochondrial impairment and neuroinflammation could be consequences of a number of molecular and biological “triggers” and could, in turn, result in a variety of downstream pathological effects. An important goal of future research will be to define the precise sequence of events that underlie neuronal injury associated with mitochondrial dysfunction and neuroinflammation. I believe that a major turning point in our understanding of Parkinson’s was the discovery of alpha-synuclein 20 years ago. Alpha-synuclein is a protein quite abundant in the normal brain. It is now generally accepted that it also plays a critical role in Parkinson’s development and progression. Despite intense research focusing on alpha-synuclein over the past several years, fundamental questions concerning alpha-synuclein-induced pathology remain unanswered. It is unclear, for example, what makes a protein present in the normal brain switch into gaining toxic/pathological properties. It is also unclear how alpha-synuclein triggers or contributes to neurodegenerative processes in Parkinson’s. A major challenge of our current research is to provide precise answers to these critical questions.
Why is PD-MitoQUANT an exciting project?
PD-MitoQUANT represents a concrete endeavour focused on the scientific questions underscored above. The two key words of the project are “mitochondria” and “alpha-synuclein”. Mitochondria, the generators of cellular energy, are important organelles in all cell types but exert an even more critical role within neuronal cells. This is because neurons are highly active cells and require constant and high supplies of energy for their function. It is not surprising therefore that a mitochondrial impairment would have deleterious consequences on neurons and has long been suspected to play a significant role in neurodegenerative processes. Alpha-synuclein pathology is a hallmark of Parkinson’s since, for example, intraneuronal deposition of aggregated alpha-synuclein is observed in Parkinson’s brain and becomes more severe in parallel to disease progression. The fundamental questions at the core of PD-MitoQUANT are: Is there a relationship between mitochondrial dysfunction and alpha-synuclein pathology? Could the accumulation of alpha-synuclein pathology lead to neuronal demise through impairment of mitochondrial function? And, could therapeutic intervention targeting mitochondria ultimately prevent or alleviate the development and consequences of alpha-synuclein pathology? All members of the teams participating in the PD-MitoQUANT project are very much aware that these are ambitious research questions. I also believe, however, that the structure and organization of this project, promoted by the European Innovative Medicines Initiative, are tremendous strengths that create the best premises for its success. I refer in particular to the fact that PD-MitoQUANT brings together experts from academia, leading research institutions, pharmaceutical companies and, as importantly, a patient advocacy organization.
Read Dino’s DZNE interview for World Parkinson Day 2019 and the launch of PD-MitoQUANT here.