PhD Scientific Days 2025

Poster Session I. - I: Theoretical and Translational Medicine

NEURO-iN: Neuronal rejuvenation in induced neurons

Name of the presenter

Pillár Vivien

Institute/workplace of the presenter

HCEMM-SU Neurobiology and Neurodegenerative Diseases Research Group, Semmelweis University, Budapest, HU

Authors

Vivien Pillár¹, Ágnes Varga², Anikó Göblös³, Lajos Kemény³, Csaba Kerepesi¹, Karolina Pircs^1,2,4

1: HUN-REN-SZTAKI-SU Rejuvenation Research Group, Budapest, HU
2: HCEMM-SU Neurobiology and Neurodegenerative Diseases Research Group, Semmelweis University, Budapest, HU
3: HCEMM-Szeged University, Szeged, HU
4: Laboratory of Molecular Neurogenetics, Lund University, Lund, SE

Text of the abstract

Neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's are becoming an increasingly severe global issue and could become the leading causes of death in developed countries by 2050. Diseases associated with dementia impose a significant burden on society. Given that these conditions are currently incurable, it is essential to investigate the molecular processes of neurons, particularly mechanisms related to autophagy and synaptic connections. The main goal of our project is to study the changes occurring in the aging processes of human neurons and to identify therapeutic targets that may delay or even reverse the progression of neurodegenerative diseases. In our experiments, we generate induced neurons (iNs) through direct reprogramming of human fibroblast cells, preserving the genetic and epigenetic aging characteristics of the donor. We have developed lentiviruses that are able to express mCherry and TagBFP, allowing us to distinguish young and aged cells using fluorescence-activated cell sorting (FACS). By mixing fibroblasts from 5 young and 5 aged donors and reprogramming them into iNs, we aim to investigate whether the young cells and milieu can rejuvenate aged iNs. We will analyse the mixed iN cultures using DNA methylation arrays and RNA sequencing, to define their biological age using transcriptomic and epigenetic clocks, as well as examining them with automated microscopy and patch-clamp electrophysiology measurements.Our experiments can significantly contribute to the identification of therapeutic targets for neurodegenerative diseases and to the establishment of new treatment options aimed at neuronal rejuvenation.