A. Prigione

Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids

Carmen Menacho, Satoshi Okawa, Iris Álvarez‐Merz, Annika Wittich et autres

Leigh syndrome (Leigh) is an untreatable mitochondrial disorder characterized by lactic acidosis and basal ganglia and midbrain pathology, leading to psychomotor regression and early death. We previously uncovered impaired neuronal morphogenesis in Leigh cerebral organoids carrying SURF1 gene variants. Leveraging this phenotype, …

Human organoids: Fit for drug discovery?

Annika Wittich, Kim Krieg, Philip Gribbon, Jakob J. Metzger et autres

Organoids are self-organizing three-dimensional (3D) in vitro tissues derived from pluripotent stem cells (PSCs) that recapitulate key structural and functional features of human organs. Their multicellular architecture and physiological relevance make them promising new approach methodologies (NAMs) for disease modeling, drug discovery, …

iPSC-derived 2D and 3D models of mitochondrial disease reveal early defects in neuronal morphogenesis and identify intervention strategies

G. Inak, A. Rybak, P. Lisowski, T.M. Pentimalli et autres

Our understanding of the mechanisms underlying the human neuronal pathology associated with impaired oxidative phosphorylation (OXPHOS) is hampered by a lack of effective model systems. Using patient-derived induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 engineering, we developed a human model of Leigh …

Genomics of Brain Aging: Nuclear and Mitochondrial Genomes☆

S. Sahdeo, A. Prigione, G. Cortopassi

Stem Cells

A. Prigione, B. Fauler, R. Lurz, H. Lehrach et autres

The ability of stem cells to propagate indefinitely is believed to occur via the fine modulation of pathways commonly involved in cellular senescence, including the telomerase, the p53, and the mitochondrial/oxidative stress pathways. Induced pluripotent stem cells (iPSCs) are a novel stem …

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Int J Dev Biol

A. Prigione, J. Adjaye

Reprogramming somatic cells to induced pluripotent stem (iPS) cells transforms differentiated cells to an embryonic stem (ES) cell-like state characterized by the acquisition of pluripotency and self-renewal capabilities. We recently demonstrated that human ES and iPS cells share similar mitochondrial properties and …

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