December NVF webinar 15th of December 2021, 16:00 CET, Prof. Martina Schmidt and Nad’a Majernikova
Dear all, Our NVF webinars continues and we are pleased to inform you that this month on the 15th of December, 16:00 CET, we have two speakers from Groningen, Prof. Martina Schmidt and PhD candidate Naďa Majerníková.
Prof. Martina Schmidt, Department of Molecular Pharmacology, University of Groningen
Title: Pharmacological targeting of nanocompartments in COPD and Alzheimer’s disease.
Abstract: Chronic diseases afflict millions of people of our worldwide aging society causing individual suffering and an enormous economic burden on our health care system. Chronic obstructive pulmonary disease (COPD) and Alzheimer’s dementia are common chronic diseases threatening the world population. COPD and Alzheimer’s dementia show tissue degeneration, inflammation and oxidative stress. Environmental stressors such as air pollutants and smoke are traditionally linked to COPD. Recent research had shown that people living in highly polluted areas have a higher risk in developing Alzheimer’s dementia. Despite the global impact of COPD and Alzheimer’s dementia, there have been very limited breakthroughs in our understanding and insights into the underlying mechanisms into their causes, treatment or cure. Clustering of cyclic nucleotide (and calcium) signaling in defined subcellular compartments/microdomains (signalosomes) has developed as a promising route to pursue to shed light into the mechanism enabling cells to exert their highly specialized tasks. Drugs used to alleviate COPD and Alzheimer’s dementia symptoms are beta-agonists and phosphodiesterase (PDE) inhibitors. The molecular drug targets of these drugs – beta-adrenergic receptors and PDEs – are key players in compartmentalization.
Our research team enrolled unconventional compartment players such as A-kinase anchoring proteins and exchange proteins directly activated by cAMP, and yet to be further characterized targets. We showed that endogenous signaling properties of these multi-protein complexes define drug action – processes being disturbed under disease conditions. To increase the probability to reprogram these multi-protein complexes and to subsequently restore their cellular function, we used approved drugs in combination with novel druggable components to achieve direct pharmacological targeting of nanocompartments. Our concept potentially not only holds for COPD and Alzheimer’s dementia but also for other chronic diseases.
I reach out to colleagues – both at university and company settings – to share knowledge, tools and compounds to develop novel compartmentalized treatment strategies.
Naďa Majerníková, Department of Molecular Pharmacology, University of Groningen and UMCG
Title: Underlying mechanisms of ferroptosis in Alzheimer’s disease.
Abstract: Alzheimer’s disease (AD), the most common form of dementia, currently affects 40–50 million people worldwide. Despite the extensive research into amyloid β (Aβ) deposition and tau protein hyperphosphorylation (p-tau), an effective treatment to stop or slow down the progression of neurodegeneration is missing. Emerging evidence suggests that ferroptosis, an iron-dependent and lipid peroxidation-driven type of programmed cell death, contributes to neurodegeneration in AD. Therefore, how to intervene against ferroptosis in the context of AD has become one of the questions addressed by studies aiming to develop novel therapeutic strategies. However, the underlying molecular mechanism of ferroptosis in AD, when ferroptosis occurs in the disease course, and which ferroptosis-related genes are differentially expressed in AD remains to be established. Our objectives are to 1. analyze which ferroptosis-related genes are differentially expressed in AD brain dependent on cell type, disease progression and gender, and 2. to compare the expression of ferroptotic markers between a) white and grey matter, b) Aβ versus non Aβ areas containing areas and c) high p-tau versus low p-tau-related areas of human post-mortem brains. Future studies should focus on developing new tools able to demonstrate where and when cells undergo ferroptosis in AD brain and build more translatable AD models for identifying anti-ferroptotic agents able to slow down neurodegeneration.