Talk
Ameliorating cellular stress in neurodegeneration
At the Human Cell Forum 2025, Dr Metzakopian shared how he used human iPSC-derived neurons powered by opti-ox in large-scale CRISPR screens to identify novel targets to restore cellular balance in Alzheimer鈥檚 and Parkinson鈥檚 disease.
At the Human Cell Forum 2025, Dr Metzakopian shared how he used human iPSC-derived neurons powered by opti-ox in large-scale CRISPR screens to identify novel targets to restore cellular balance in Alzheimer鈥檚 and Parkinson鈥檚 disease.
Neurodegenerative diseases such as Alzheimer鈥檚 (AD) and Parkinson鈥檚 (PD) are marked by progressive neuronal loss and lack effective disease-modifying therapies. A common thread across these disorders is chronic cellular stress, including oxidative and ER stress, which drives damage through mechanisms like lipid peroxidation and protein misfolding. We aim to decode and restore stress-related homeostasis in AD by leveraging hypothesis-free CRISPR screens in iPSC-derived human neurons. Building on screens targeting oxidative stress, ER stress, and RBM3 cold shock protein, we have uncovered novel, actionable targets. These discoveries are made possible through the development and application of physiologically relevant in vitro models鈥攖ools that will be further discussed during this presentation.