How did your interest in biochemistry, chemistry and pharmacology originate, and how has your academic and scientific journey in these fields developed to date?
My interest in Biological Sciences and Chemistry began at an early age, but it was during secondary education that this interest truly solidified, largely thanks to teachers who instilled a passion for scientific research. My indecision between Biological Sciences and Chemistry led me to enrol in 2008 in the Biochemistry undergraduate programme at the Faculty of Sciences of the University of Porto (FCUP). Today, I am certain that it was the best choice. During my academic journey, I discovered Organic Chemistry, which fascinated me from the start due to its complexity and its potential biomedical applications. However, it was only towards the end of my undergraduate studies and during the internship I carried out at the Organic Chemistry Research Laboratories at FCUP that I discovered "my element": Medicinal Chemistry. It is the ability to create new molecules with undiscovered properties that makes Chemistry, and particularly Medicinal Chemistry, a stimulating and challenging field. Naturally, I pursued a Master’s in Biochemistry at FCUP, which enabled me to gain expertise in pharmacology and establish a link with Medicinal Chemistry. Later, in 2018, I completed my PhD in Sustainable Chemistry, which opened my eyes to a more responsible use of Chemistry as a tool for the production of bioactive molecules. I had the opportunity to make my mark by developing more sustainable synthesis methodologies in the field of peptide chemistry. It is an added challenge, but one that should govern all processes led by modern chemists.

Much of your scientific work has been focused on neurodegenerative diseases. What is behind this particular interest, especially in relation to Parkinson’s disease?
Neurodegenerative diseases are an emerging problem, for which effective treatments to stop the disease’s progression do not yet exist. Technological and scientific advances, coupled with improved infrastructure and quality of life in general, inevitably lead to an increase in average life expectancy. However, advanced age is also associated with an increased risk of developing neurodegenerative diseases of the central nervous system, such as Alzheimer’s and Parkinson’s. These diseases represent a significant challenge for modern societies and it is expected that their prevalence will significantly increase over the coming decades. Thus, the development of new therapeutic alternatives to mitigate symptoms, improve patients' quality of life, ultimately preventing and/or slowing disease progression, has become urgent. During my academic journey, I explored different lines of research focused on rescuing the potential of biomolecules that naturally exist in our body and possess activity against neurodegenerative diseases. However, they’ve been overlooked as potential drug candidates. One such molecule is melanostatin, a small neuropeptide that exhibits anti-Parkinson’s activity and has a different mechanism of action than approved drugs used in the treatment of the disease. However, due to gastrointestinal absorption problems and reduced biochemical stability, melanostatin has been neglected as a potential Parkinson’s drug. This led to the challenge of using Medicinal Chemistry to rescue the therapeutic potential of this neuropeptide for Parkinson’s therapy.

You lead the DynaPro team, a project focused on developing a new drug for Parkinson’s treatment, one that is more efficient and has fewer side effects than those currently used. What scientific discoveries underlie this research, and how is this drug different?
In Parkinson’s disease, there is a loss of dopaminergic neurons, that are responsible for producing dopamine. As the disease progresses, dopamine levels in the central nervous system decrease, impairing the activation of dopamine receptors and, consequently, the dopaminergic pathways. This results in both motor and non-motor symptoms. Current therapies counteract dopamine depletion by using levodopa (a dopamine precursor), dopamine agonists, and inhibitors of the main enzymes involved in dopamine and levodopa metabolism. However, over time, this type of treatment loses effectiveness, requiring increasingly larger pharmacological doses, which leads to serious side effects that can even worsen symptoms. In contrast to most pharmacological strategies that focus on increasing dopamine levels in the central nervous system, our research team is exploring the modulation of dopamine receptors. Melanostatin is an endogenous neuropeptide that binds to these receptors and enhances dopamine’s effects. This means receptors can be activated at lower dopamine levels, making it clinically significant for Parkinson’s disease. Nevertheless, despite its therapeutic potential, melanostatin has low stability in neuronal tissues and poor gastrointestinal permeability, limiting its clinical translation. Therefore, the primary aim of this project is to rescue melanostatin for use in Parkinson’s therapy by developing more potent analogues with pharmacokinetic properties, that allow progression into preclinical studies.

How do you expect this new treatment to positively impact the lives of those living with Parkinson’s?
Although levodopa is very effective in controlling motor symptoms in the early stages of Parkinson’s, it loses efficacy over time while requiring increasingly high doses, which invariably lead to side effects that can even worsen motor symptoms, such as levodopa-induced dyskinesias. This has a very negative impact on the lives of patients, limiting their quality of life and the clinical utility of the drug. Allosteric modulators of dopamine receptors, such as melanostatin and its derivatives, could represent a viable pharmacological alternative because their effects only occur in the presence of dopamine, thereby avoiding relevant side effects. In the early stages of the disease, when dopamine levels are still relatively high, these modulators can maximise dopamine’s effects by ensuring dopaminergic circuit activation. This could delay the initiation of levodopa treatment until later stages of the disease. Conversely, once levodopa is introduced, allosteric modulators could reduce the pharmacological doses required, allowing levodopa to be used more safely and for longer periods, improving the patient’s quality of life.

What are the greatest challenges in leading a scientific research project, and how do you approach and overcome obstacles?
The technical and scientific expertise of a research team are important for conceiving innovative projects with the potential to make scientific and technological advances with direct societal impact. However, these alone are insufficient for a scientific project to reach its full potential. Leading a research project entails challenges that extend beyond those inherently linked to scientific investigation. Running research projects requires leadership and management skills, which are fundamental for coordinating research teams and using resources, which are often limited, more efficiently. In this regard, collaboration between institutions not only accelerates knowledge transfer but can also address technical needs through resource sharing. Additionally, engaging the community and potential investors is also the responsibility of research leaders, in order to ensure the continuation of projects after initial funding ends. This involves participation in conferences, workshops and science dissemination. Leadership must anticipate problems, ensure objectives are met and foster a stimulating team environment while maintaining long-term focus.

What examples of interdisciplinary collaborations would you highlight in research projects, and how do they contribute to multidisciplinary approaches and knowledge transfer?
Interdisciplinary collaborations are vital in research projects to drive scientific progress and innovative solutions to complex problems such as neurodegenerative diseases. Multidisciplinary combines different perspectives and methodologies, while knowledge transfer between disciplines fosters innovation and reveals new research avenues. For the development of more selective and safe drugs targeting the central nervous system, collaboration across fields such as molecular biology and medicinal chemistry is essential. Biologists identify biological targets and develop models to study underlying disease mechanisms, while chemists conduct molecular refinement based on biological data. Such collaborative work among scientists from diverse fields creates more effective and comprehensive solutions.

In your opinion, what is the most critical factor to ensure that the general public understands neurodegenerative diseases and their treatments?
A central aspect for society to develop greater awareness of neurodegenerative diseases, their treatments, and the impact on affected individuals and their families is, invariably, education. In this context, the role of researchers and science communicators is of utmost importance, contributing to scientific literacy and bringing society closer to neuroscience research and its challenges through clear and effective communication. Investing in education and literacy in neuroscience directly fosters societal awareness of the importance of basic and applied research in developing more effective treatments for neurodegenerative diseases. Access to information and the involvement of all sectors of society are fundamental pillars for understanding these diseases and their treatments, promoting a more inclusive and empathetic society with greater resilience to face these complex challenges.

What can we collectively do to ensure the best possible quality of life and, above all, prevent the incidence of these debilitating diseases?
To ensure the best possible quality of life and prevent the incidence of neurodegenerative diseases, we must collectively adopt a multifaceted approach that includes promoting healthy lifestyles, education and awareness, effective public policies, social support, and investment in scientific research. It begins early, with health education in school curricula and the promotion of healthy habits. It also involves implementing urban planning policies that encourage physical activity and social interaction, such as green spaces, while limiting exposure to environmental toxins linked to neurodegenerative diseases. For instance, in the case of Parkinson’s disease, exposure to certain pesticides is closely associated with an increased risk of developing the condition. Investment in basic and applied research is essential for better understanding the causes, treatments, and preventive measures for neurodegenerative diseases. By addressing all these aspects, we can create a healthier and more resilient society, capable of proactively tackling the challenges posed by neurodegenerative diseases.

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