PhD Scientific Days 2026
Budapest, 16-18 June 2026
Poster Session 1.I - Theoretical and Translational Medicine
Hunting for drugs: repurposing for AMPK targeting in Huntington’s disease
Előadó neve
Balázs, Kis, MSc
Neptune code
EM3216
Előadó munkahelye
Semmelweis University, Institute of Clinical Pathophysiology
Előadó telefonszáma
+36 1 459-1500/60369
Előadó e-mail címe
kis.balazs@semmelweis.hu
Az előadás címe
Hunting for drugs: repurposing for AMPK targeting in Huntington’s disease
Szerző(k) neve és munkahelye
Balázs Kis1, Melinda E. Gazdik1,2, Ágnes Varga1, Daniella Hühn3, Anikó Göblös4, Roger A. Barker5, Lajos Kemény4, Attila Szűcs1,2, Oscar Fernandez-Capetillo3,6, Karri Lamsa7, Karolina Pircs1,8
1: HCEMM-SU Neurobiology and neurodegenerative diseases, Institute of Clinical Pathophysiology, Semmelweis University, Budapest, Hungary.
2: Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary
3: Science for Life Laboratory, Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 21, Stockholm, Sweden
4: HCEMM-USZ, Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary
5: Wellcome-MRC Cambridge Stem Cell Institute & John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
6: Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid, 28029, Spain
7: HCEMM-USZ, Human neuron physiology and therapy Core Group, Szeged, Hungary
8: Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem
Bemutatás módja
Poszter
Szekció
Poster Session 1.I - Theoretical and Translational Medicine
Language of the presentation
English
Preferred session
Theoretical and Translational Medicine
Összefoglaló szövege
Neurons are among the most energy-demanding cell types in the human body; therefore, disruptions in cellular energy metabolism disproportionately affect neuronal viability and function. Neurodegenerative diseases are increasingly understood to impose chronic energetic stress on neurons, either as a downstream consequence of pathology or as a contributing driver of disease progression. In Huntington’s disease (HD), we employed a human, patient-derived, disease-specific induced neuronal (iN) model and identified a significant dysregulation in several parts of the AMP-activated protein kinase (AMPK) signaling pathway. Proper AMPK signaling has been consistently shown to exert neuroprotective effects across multiple HD models. AMPK functions as a key cellular energy sensor by monitoring the intracellular ATP/AMP ratio and responds to energetic deficits by promoting catabolic processes such as autophagy, stimulating mitochondrial biogenesis, and suppressing energy-consuming anabolic pathways.
This project aims to repurpose FDA-approved drugs to target dysregulated components of the AMPK pathway. Using a viability assay, we identified 89 protective compounds from a 2,400-compound EMBL library in an HD cellular model (U2OSQ94). To isolate specific AMPK activators, we are screening hits with the ExRAI-AMPKAR sensor. Compounds with FDA and EMA approval, current availability, and minimal side effects were prioritized, resulting in five candidates: salsalate, olmesartan, nifedipine, levodopa, and acetylcysteine. These will be tested in HD_iNs to assess effects on neuronal morphology (TAU), mitochondria (MitoTracker™ Deep Red), AMPK (α-subunit), and neuronal function via whole-cell patch-clamp electrophysiology. We will also use qPCR to assess treatment-induced changes in the expression of genes dysregulated in the AMPK pathway, along with changes in HTT expression.
Concurrently with the screening we are in contact with clinics to further verify that our compounds are safe for HD patient prescription.
University
Semmelweis University
Supervisor
Pircs Karolina
Publication of my abstract
I do not give consent to the publication of my abstract on the website of the congress.
phd.section.field
in doctoral studies after complex exam (PhD)
Kind
Szabad
Status
elfogadva
Accepted presentation method
poszter
Előadás fájl jóváhagyás
nem rendelkezett róla
Előadó
7420
Start
16:54
End
16:57