{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T17:48:35Z","timestamp":1782409715528,"version":"3.54.5"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":175,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research"},{"name":"BMBF TreatHSP consortium","award":["01GM1905B"],"award-info":[{"award-number":["01GM1905B"]}]},{"name":"BMBF TreatHSP consortium","award":["01GM2209B"],"award-info":[{"award-number":["01GM2209B"]}]},{"name":"ACS iIMMUNE","award":["01EO2105"],"award-info":[{"award-number":["01EO2105"]}]},{"name":"\u2018Neurodevelopment and Vulnerability of the Central Nervous System\u2019"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["270949263"],"award-info":[{"award-number":["270949263"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK2162"],"award-info":[{"award-number":["GRK2162"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["505539112"],"award-info":[{"award-number":["505539112"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021711","name":"Bavarian Ministry of Science and the Arts","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ForInter network"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Biallelic pathogenic variants in SPG7 are a frequent cause of hereditary spastic paraplegia leading to progressive disability due to a length-dependent degeneration of cerebellar and cortical projection neurons. While underlying mechanisms have been linked to impaired mitochondrial function, no disease-modifying therapy is available. We generated induced pluripotent stem cell\u2013derived cortical neurons from SPG7 patients with non-sense or truncating variants and from matched controls. We performed detailed phenotyping of neuronal differentiation, as well as mitochondrial and neuritic morphology and function. We explored the effects of Bz-423, a modulator of the mitochondrial permeability transition pore, as a potential rescue of SPG7-specific cellular phenotypes. We successfully differentiated SPG7 patient-derived neurons, without quantitative differences in differentiation compared with controls. However, we delineate neurite-specific aberrations of mitochondrial morphology and ultrastructure. Moreover, anterograde axonal mitochondrial transport was impaired in SPG7. Exposure to Bz-423 rescued ultrastructural and functional phenotypes. In summary, our data show impaired neuritic mitochondria in a patient-specific human model, and we here demonstrate for the first time beneficial effects of Bz-423 on neuritic ultrastructure and function in a human neuronal SPG7 system. Moreover, we identify the mitochondrial permeability transition pore as a molecular target to rescue phenotypes also in carriers of non-sense or truncating SPG7 variants.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag219","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:57:47Z","timestamp":1782302267000},"source":"Crossref","is-referenced-by-count":0,"title":["Rescue of mitochondrial and neurite pathology in\n                    <i>SPG7<\/i>\n                    hereditary spastic paraplegia patient-derived cortical neurons"],"prefix":"10.1093","volume":"8","author":[{"given":"David","family":"Neubauer","sequence":"first","affiliation":[{"name":"Department of Stem Cell Biology, Friedrich-Alexander-Universita\u0308t (FAU) Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Kai\u00dfer","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, Friedrich-Alexander-Universita\u0308t (FAU) Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]},{"name":"Department of Molecular Neurology, FAU Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Krumm","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, Friedrich-Alexander-Universita\u0308t (FAU) Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Boerstler","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, Friedrich-Alexander-Universita\u0308t (FAU) Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Metzner","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, Friedrich-Alexander-Universita\u0308t (FAU) Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamer","family":"Al Hamad","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, Friedrich-Alexander-Universita\u0308t (FAU) Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Bo\u0308ttcher","sequence":"additional","affiliation":[{"name":"Health Campus for Inflammation, Immunity and Infection (GCI3), Otto-von-Guericke University Magdeburg , Magdeburg 39120 ,","place":["Germany"]},{"name":"Department of Hematology, Oncology, Cell and Radiation Therapy, Otto-von-Guericke University Magdeburg , Magdeburg 39120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Gei\u00dfler","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, Friedrich-Alexander-Universita\u0308t (FAU) Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Prots","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, Friedrich-Alexander-Universita\u0308t (FAU) Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]},{"name":"Department of Conservative Dentistry and Periodontology, FAU Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Arnold","sequence":"additional","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, FAU Erlangen-N\u00fcrnberg , Erlangen 91054 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Mougiakakos","sequence":"additional","affiliation":[{"name":"Health Campus for Inflammation, Immunity and Infection (GCI3), Otto-von-Guericke University Magdeburg , Magdeburg 39120 ,","place":["Germany"]},{"name":"Department of Hematology, Oncology, Cell and Radiation Therapy, Otto-von-Guericke University Magdeburg , Magdeburg 39120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology, FAU Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Winner","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, Friedrich-Alexander-Universita\u0308t (FAU) Erlangen-Nu\u0308rnberg , Erlangen 91054 ,","place":["Germany"]},{"name":"Center for Rare Diseases Erlangen (ZSEER), University Hospital Erlangen , Erlangen 91054 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