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Schmidt, S. ; Luecken, M. ; Trümbach, D. ; Hembach, S. ; Niedermeier, K.M. ; Wenck, N. ; Pflügler, K. ; Stautner, C. ; Böttcher, A. ; Lickert, H. ; Ramirez Suastegui, C. ; Ahmad, R.* ; Ziller, M.J.* ; Fitzgerald, J.C.* ; Ruf, V.* ; van de Berg, W.D.J.* ; Jonker, A.J.* ; Gasser, T.* ; Winner, B.* ; Winkler, J.* ; Weisenhorn, D.M. ; Giesert, F. ; Theis, F.J. ; Wurst, W.

Primary cilia and SHH signaling impairments in human and mouse models of Parkinson's disease.

Nat. Commun. 13:4819 (2022)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
Parkinson's disease (PD) as a progressive neurodegenerative disorder arises from multiple genetic and environmental factors. However, underlying pathological mechanisms remain poorly understood. Using multiplexed single-cell transcriptomics, we analyze human neural precursor cells (hNPCs) from sporadic PD (sPD) patients. Alterations in gene expression appear in pathways related to primary cilia (PC). Accordingly, in these hiPSC-derived hNPCs and neurons, we observe a shortening of PC. Additionally, we detect a shortening of PC in PINK1-deficient human cellular and mouse models of familial PD. Furthermore, in sPD models, the shortening of PC is accompanied by increased Sonic Hedgehog (SHH) signal transduction. Inhibition of this pathway rescues the alterations in PC morphology and mitochondrial dysfunction. Thus, increased SHH activity due to ciliary dysfunction may be required for the development of pathoetiological phenotypes observed in sPD like mitochondrial dysfunction. Inhibiting overactive SHH signaling may be a potential neuroprotective therapy for sPD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 13, Heft: 1, Seiten: , Artikelnummer: 4819 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed