What initially sparked your interest in Pharmacology, the field in which you trained, and how did your scientific career develop over time?
My interest in Pharmacology stems from a curiosity to understand how medicines work and from a desire to discover treatments for disease. I suppose that childhood play (with a microscope and a chemistry kit used to test dyes on the paramecia found in the water jars of my mother’s flowers) together with a handful of excellent mathematics, chemistry and biology teachers during secondary school, influenced my decision to study Pharmaceutical Sciences at the University of Porto. At the end of my degree, I had my first international experience, during which I fell in love with Neuroscience. In Madrid, I came into contact with rare neurological diseases and was fascinated by how mutations in a single gene can drastically disrupt the functioning of the nervous system. I combined Pharmacology with Neuroscience by undertaking a PhD focused on the pathophysiology and experimental treatments of Huntington’s neurodegenerative disease. At the Centre for Neuroscience in Coimbra and at the Buck Institute in California, I expanded the experience I had gained in Porto and Madrid and found inspiration to further develop my scientific career. After completing my PhD, as a lecturer at the Faculty of Pharmacy of the University of Porto (FFUP), I continued to deepen my engagement with Pharmacology as the coordinator of this curricular unit and founded the Neuroscience curricular unit. Another important step in my career was establishing my own research team. This required securing project funding as principal investigator, equipping the laboratory, training doctoral students and building an international collaborative network, particularly in England, where I have regularly travelled since 2009 for scientific collaborations and teaching.

You coordinate the Disease Pathways & Biomarkers research group at UCIBIO and are the founder and leader of the Mitochondria and Neurobiology laboratory. Why are mitochondria so central to understanding brain ageing and neurodegeneration, and how has this approach guided your team’s research?
Mitochondria perform multiple functions that are critical to proper brain function; primary or secondary failures in these functions accelerate ageing and neurodegeneration. A well-nourished and developed brain not only unconsciously regulates bodily functions but is also responsible for consciousness: it enables empathy, regulates emotions, travels through time via memories, imagines the future and coordinates our actions. All of these cerebral activities require vast amounts of energy, which is largely produced by mitochondria. For this reason, the brain is particularly vulnerable to failures in energy production and in the distribution of mitochondria across neuronal networks, as well as to defects in mitochondrial renewal and the selective degradation of dysfunctional mitochondria. My interest lies in the mechanisms underlying these failures and in the identification and validation of therapeutic targets. In my team, we work with models of neurodegenerative diseases associated with mitochondrial dysfunction and strong motor impairment, such as Parkinson’s disease, Huntington’s disease and Amyotrophic Lateral Sclerosis. We also study primary mitochondrial diseases caused by genetic mutations. We are particularly interested in mechanisms of selective vulnerability, that is, how different mutant proteins or mitochondrial toxins, when present throughout the nervous system, affect some neuronal populations more than others. Characterising these mechanisms has the potential to identify disease-modifying therapeutic targets. Accordingly, we have also been investigating experimental therapies, including drugs capable of modulating epigenetics, protein degradation pathways and mitochondrial functions.

Regarding pathophysiology and the development of experimental therapeutic approaches, which biological mechanisms do you currently consider most critical in the progression of neurodegenerative diseases, and where do you see the greatest therapeutic potential in the short to medium term?
I consider mechanisms associated with the loss of protein homeostasis and mitochondrial dysfunction to be particularly relevant, as they are common to several neurodegenerative diseases regardless of their primary cause, which in many cases remains unknown and is likely multifactorial. The neuropathology of many of these diseases includes the progressive accumulation of protein aggregates, with or without a causal mutation. Protein aggregation has mixed effects: on the one hand, it sequesters and reduces levels of toxic proteins; on the other, it depletes components of the protein homeostasis machinery and induces physical blockages to intracellular dynamics. It is still unclear whether preventing protein aggregation is necessarily beneficial. There is greater consensus around reducing levels of free toxic protein species. This approach is the subject of active research, with experimental therapies that modulate the activity of molecular chaperones and degradation pathways such as autophagy and the ubiquitin–proteasome system. With regard to mitochondrial dysfunction, research initially focused on bioenergetic alterations and oxidative stress but has expanded to include dynamic processes such as mitochondrial fission, fusion and transport, which are all critical for the distribution and quality control of these cellular resources in highly polarised cells like neurons. More recently, mechanisms involved in the identification and degradation of dysfunctional mitochondria through mitophagy have emerged as therapeutic targets, although sufficiently selective modulation strategies are still lacking. In both proteostasis regulation and mitochondrial function, there are ongoing clinical trials that may enable therapeutic interventions in the medium term.

Still in the context of neurodegenerative diseases, which recent scientific advances do you consider most promising? Conversely, what are the main challenges that hinder faster translation of research advances into clinical practice?
Advances in gene therapy that allow mutated genes to be replaced or corrected seem particularly promising. In theory, they can modify disease progression or even lead to cures. However, neurodegenerative diseases are generally diagnosed after irreversible damage to neuronal networks has occurred. Even with cellular and gene therapies, repairing the loss of neurons integrated into networks with thousands of dynamic connections is extremely difficult. In the minority of cases where the cause is known in advance and is monogenic, it is already possible to prevent transmission to the next generation or to limit neuronal network damage if therapy is initiated very early. In late diagnoses, success is more limited, but there have been advances in pharmaceutical formulations for improved symptom control, robotic prostheses and the implantation of deep brain stimulation electrodes that enhance quality of life. We have seen several promising preclinical results with new therapies that rescue phenotypes and extend lifespan. However, such results are rarely observed in clinical trials. The main challenges relate to the heterogeneity of causal factors in humans and to ageing, which is not compatible with preclinical trials. A human may be born with a causal mutation for a neurodegenerative disease and only develop symptoms after the age of 50. Preclinical trials, however, require models that manifest symptoms within weeks or months, resulting in accelerated pathologies driven by factors that may not align with human disease. To improve translation, it is essential to deepen our understanding of pathophysiological mechanisms and use this knowledge to enhance the validity of preclinical models.

The growing use of data, computational analysis and digital tools has been transforming both biomedical research and education. What role do you attribute to data science and generative artificial intelligence in advancing neuroscience research in the coming years?
Data science, particularly the ability to analyse large volumes of heterogeneous data (text, numerical or image-based) from multiple sources, is now an integral part of the research process. Time previously spent processing data through manual input software and drop-down menus can now be saved using programming languages supported by generative artificial intelligence. However, this has increased the demand for us, as humans, to develop our real intelligence (both cognitive and emotional) in order to understand and make conscious decisions about increasingly abundant and diverse data. Otherwise, we risk becoming mere agents of decisions made by artificial entities. Neuroscience research is being driven forward by the integration of brain imaging structural and functional data, with genomic, transcriptomic, proteomic and metabolomic data. The integration of these datasets using generative AI has supported the development of diagnostic and disease progression biomarkers, improved understanding of pathophysiology and the creation of predictive models. Additionally, these models now allow computer simulations that support hypothesis selection and pharmacological options for testing in real laboratory environments, accelerating therapeutic development. Artificial intelligence has also advanced cognitive neuroscience. Concerns regarding the reliability and hallucinations of generative AI have encouraged more objective reflection on human confabulation. In reality, the reliability of a human narrative also depends on the data on which it is based and on the sophistication of the mental models it employs.

If you had to identify one major scientific or pedagogical priority for the next decade, which do you believe will be decisive for the future of neuroscience and Health Sciences education, particularly in the context of a One Health approach?
One Health is a holistic vision that interconnects human, animal and environmental health. From a neuroscience perspective, an individual’s ability to follow One Health principles depends on their cognitive and emotional maturity. What is the value of communicating a holistic health strategy if the audience lacks the willpower to follow it? I identify the development of students’ mental models as a pedagogical priority. Beyond discipline-specific models, it is essential to develop emotional intelligence. This involves, first, self-awareness, emotional monitoring and regulation; second, understanding others and managing relationships; and third, recognising that we share the same planet, are interdependent, and require limits and commitments to achieve sustainability and maximise health and well-being. To promote One Health, legislative action is crucial: discouraging the misuse of pesticides, antibiotics and other animal growth promoters, and requiring transparency in nutritional labelling and in products such as alcohol and tobacco. Equally important is educational action: fostering societies enriched with empathetic individuals who understand One Health interdependence and make sound individual and collective decisions. These skills can be developed through targeted emotional intelligence training, collaborative projects and volunteering. The combination of emotional intelligence with technical skills will continue to drive scientific innovation, enabling more affordable and healthier alternatives and supporting sustainable changes that promote One Health.

In addition to research, you coordinate the U.Porto Observatory for Academic Success and have been recognised for your pedagogical work. How do you integrate research, teaching and academic policy, and what challenges do you currently identify in promoting student success and well-being in higher education?
I am able to integrate my research and teaching because they are in complementary areas, but managing the time management is still a challenge. Regarding academic policy, my experience in university management and the implementation of pedagogical innovations has been helpful. At the Observatory, we give visibility to work carried out at U.Porto and conduct studies to propose evidence-based measures. Some studies involve cognitive neuroscience, testing hypotheses and measuring parameters such as student competencies. Others are purely observational, without the possibility of demonstrating causality, but allow us to quantify, identify and study associated factors, such as student dropout. Currently, I see several challenges in promoting student success and well-being. I highlight those related to student motivation and empowerment for learning, as well as the motivation and empowerment of teaching staff for teaching and assessment. These depend on intrinsic factors such as emotional intelligence, individual priorities, empathy and willingness to build relationships. For students, extrinsic factors also play a role, such as the lack of affordable housing, which forces time-consuming commutes, in addition to time lost to excessive digital distractions at the expense of focused, structured reading that builds useful mental models. For academic staff, conflicts related to generative AI and the perception of a lack of parity of esteem between research and teaching influence investment in capacity-building for teaching and assessment methodologies and technologies. These are complex challenges, but the University of Porto is attentive and actively engaged in continuous improvement.

You maintain interests outside the laboratory: playing the guitar, cycling and exploring biodiversity. How do these activities influence, directly or indirectly, your approach to science, teaching and even concepts of health and ageing?
Physical activity, contact with nature and meditative moments such as playing the guitar contribute to my physical and psychological well-being. I regularly participate in road and trail running, which require aerobic capacity, determination and perseverance. These activities serve as self-assessment, where the relationship between training and performance is evident. Physical activities help me observe reality objectively and protect me from the self-delusion that is common in intellectual pursuits. They also make me a better teacher, particularly in Human Physiology, as they allow me to apply cardiovascular, respiratory and neuromuscular knowledge. Interestingly, before teaching at university level, I taught martial arts and guitar. At university, I have even brought my guitar into classes to generate sound waves in sensory physiology lectures and explain how we perceive different frequencies. And biodiversity? Well, a researcher in the life or health sciences knows that few theories have greater explanatory power than the theory of evolution. Reading books on evolutionary biology together with observing species in their natural habitats, is how I plan my nature-based holidays. I always keep evolutionary theory in mind when investigating physiological mechanisms and selecting organisms for disease models. When teaching Human Physiology or Neuroscience, I also apply evolutionary concepts and comparisons across species. So yes, these activities outside the laboratory clearly influence how I view science and how I practise teaching and research. As for ageing, I do not know whether they will give me more years of life, but they certainly give more life to my years.

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