NVF webinar 19th of January 2022, 16:00 CET, Prof. dr. A. Maassen van den Brink and Dr. Erwin L Roggens.

Where https://us02web.zoom.us/j/81798794396?pwd=OWJUcDFyK0c0ZFprb210ZnhKWWZDQT09

Meeting ID: 817 9879 4396

Passcode: 279051

Speaker 1:

Antoinette Maassen van den Brink, Professor of Neurovascular Pharmacology, Internal Medicine, Erasmus MC

Professor Maassen van den Brink studied Biomedical Sciences in Leiden, and then obtained her PhD at the Department of Pharmacology at the (current) Erasmus MC, studying the coronary side effects of antimigraine drugs. She currently investigates the neurovascular aspects of migraine, with a special emphasis on the role of female sex steroids. She is also the head of the Junior Med School and PI of the Academic Centre of Excellence GESTURE (gender studies). She is a board member of the Dutch Headache Society, former board member of the Dutch Pharmacology Society and founding board member of the Dutch Society for Gender and Health. Further, she serves as a board member for the European Headache Federation and the Federation of European Pharmacological Societies.

Title: Neurovascular Pharmacology of Migraine

Abstract: Migraine is a neurovascular disorder, which is classified as the second disabler by the World Health Organisation.  While recently a lot of progress has been made in the treatment of migraine, still many aspects of migraine are not understood.  Calcitonin Gene-Related Peptide is one of the key players in the pathophysiology of migraine, but many aspects of its receptor pharmacology are still to be elucidated to enable the development of safer and more effective antimigraine medication in future.

Speaker 2:

Erwin L Roggen, Managing director at ToxGenSolutions

Dr Roggens obtained a degree in Biochemistry at the University of Antwerp in 1984. He has been involved for over 18 years in development, implementation, dissemination and acceptance of alternative methods to animal testing. His long-term vision is better human and environmental health and safety through the application of non-animal approaches for testing and assessment. In line with this vision, he established 3Rs Management and Consulting (3rsmc-aps.com), SenzaGen (senzagen.com) and ToxGenSolutions (toxgensolutions.eu), providing tools for driving promising non-animal tools from the bench to industry and regulatory authorities.

Title: Application of the Adverse Outcome Pathway (AOP) concept to understand the impact of environmental risk factors on the progression of age-related memory loss leading to Alzheimer’s Disease.

Abstract: While aging and genetics are important risk factors for acquiring sporadic Alzheimer’s disease (sAD), systemic and environmental factors are increasingly recognized to contribute to this risk in a still poorly understood way. Inspired by the tau-cascade hypothesis, a tau-driven AOP towards memory loss was constructed using existing (primarily) human data selected according to predefined selection/rejection criteria. Sequences of key events (KEs) and plausible key event relationships (KERs) triggered by the bidirectional relationship between brain cholesterol and glucose dysmetabolism were captured. To portray how environmental factors may contribute to sAD progression, information on chemicals and drugs, that experimentally or epidemiologically associate with the risk of sAD were mapped on this AOP. The result suggests that chemicals may accelerate sAD progression by plugging into 26 different sAD relevant molecular initiating events (MIEs). A complex network of aging-related homeostatic pathways that are sensitive to an accelerated deterioration in the presence of risk factors is implicated in the pathogenesis of e.g., sAD. Since sAD pathology and neurotoxicity share microRNAs (miRs) regulating common as well as overlapping pathological processes, literature was searched for miRs associated with human sAD and environmental neurotoxicity. Functional miR analysis using PathDip resulted in miR-target interaction networks linked to brain cholesterol and glucose dysmetabolism as well as KEs of the tau-driven AOP. While miR analysis confirmed most of the retrieved findings, 40 miRs were found to be involved in both sAD and neurotoxicity and to dysregulate key processes of the AOP. Creating miR-target interaction networks related to the pathological processes involved in early sAD progression, and environmental chemical-induced neurotoxicity, respectively, provided overlapping miR-target interaction networks. This overlap offers an opportunity to create an alternative picture of the mechanisms underlying early sAD progression. Looking at initiation and progression of sAD from this new angle may open for new biomarkers and novel drug targets for sAD before the appearance of the first clinical symptoms.