%0 Journal Article
%A Heger, Leonie
%A Kertess, Leonie
%A Kaufhold, Clara Margarete
%A Gubinelli, Francesco
%A Cardona-Alberich, Aida
%A Özata, Gamze
%A Müller, Stephan A
%A Tschirner, Sarah K
%A Stehling, Oliver
%A Schifferer, Martina
%A Peron, Camille
%A Tiranti, Valeria
%A Lill, Roland
%A Iuso, Arcangela
%A Zecca, Luigi
%A Strupp, Michael
%A Oertel, Wolfgang
%A Lichtenthaler, Stefan F
%A Burbulla, Lena F.
%T Patient-Derived Neurons Exhibit α-Synuclein Pathology and Previously Unrecognized Major Histocompatibility Complex Class I Elevation in Mitochondrial Membrane Protein-Associated Neurodegeneration.
%J Movement disorders
%V 40
%N 12
%@ 0885-3185
%C New York, NY
%I Wiley
%M DZNE-2025-01377
%P 2811 - 2818
%D 2025
%X Mitochondrial membrane protein-associated neurodegeneration (MPAN) from the neurodegeneration with brain iron accumulation (NBIA) family is a rare neurodegenerative disease marked by α-synuclein aggregation, brain iron accumulation, and midbrain dopaminergic neuron degeneration.The mechanisms driving neuron vulnerability remain unclear. Our study aimed to develop a patient-derived disease model replicating key pathologies of patient brains.We generated induced pluripotent stem cell-derived midbrain dopaminergic neurons from MPAN patients and examined ultrastructural and biochemical markers of pathology.MPAN patient neurons displayed α-synuclein aggregation, axonal swellings, iron accumulation, and severe membrane destruction. In addition, levels of the major histocompatibility complex class I (MHC-I), linked to cellular stress and neurodegenerative processes, were elevated in patient neurons. Treatment with acetyl-leucine, a potentially neuroprotective compound, decreased MHC-I.This first patient-derived neuronal model of MPAN provides a useful tool for further research aimed at unraveling the complexities of this disease and developing potential therapeutic interventions. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
%K MPAN (Other)
%K NBIA (Other)
%K dopaminergic neurons (Other)
%K iPSC disease modeling (Other)
%K α‐synuclein (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40948186
%R 10.1002/mds.70029
%U https://pub.dzne.de/record/282916