- Titel
- Axonal Lysosomal Assays for Characterizing the Effects of LRRK2 G2019S
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa2-995940
- Quellenangabe
- Biology
Erscheinungsjahr: 2024
Jahrgang: 13
Heft: 1
E-ISSN: 2079-7737
Artikelnummer: 58 - Erstveröffentlichung
- 2024
- Abstract (EN)
- The degeneration of axon terminals before the soma, referred to as “dying back”, is a feature of Parkinson’s disease (PD). Axonal assays are needed to model early PD pathogenesis as well as identify protective therapeutics. We hypothesized that defects in axon lysosomal trafficking as well as injury repair might be important contributing factors to “dying back” pathology in PD. Since primary human PD neurons are inaccessible, we developed assays to quantify axonal trafficking and injury repair using induced pluripotent stem cell (iPSC)-derived neurons with LRRK2 G2019S, which is one of the most common known PD mutations, and isogenic controls. We observed a subtle axonal trafficking phenotype that was partially rescued by a LRRK2 inhibitor. Mutant LRRK2 neurons showed increased phosphorylated Rab10-positive lysosomes, and lysosomal membrane damage increased LRRK2-dependent Rab10 phosphorylation. Neurons with mutant LRRK2 showed a transient increase in lysosomes at axotomy injury sites. This was a pilot study that used two patient-derived lines to develop its methodology; we observed subtle phenotypes that might correlate with heterogeneity in LRRK2-PD patients. Further analysis using additional iPSC lines is needed. Therefore, our axonal lysosomal assays can potentially be used to characterize early PD pathogenesis and test possible therapeutics.
- Andere Ausgabe
- Link zum Artikel, der zuerst in der Zeitschrift „Biology” im Verlag MDPI erschienen ist.
DOI: 10.3390/biology13010058 - Verweis
- Ergänzendes Material ist unter folgendem Link zu finden.
Link: https://www.mdpi.com/2079-7737/13/1/58#app1-biology-13-00058 - Freie Schlagwörter (EN)
- axonal trafficking, LRRK2, iPS cells, Parkinson’s disease, dying back
- Klassifikation (DDC)
- 570
- Verlag
- MDPI, Basel
- Förder- / Projektangaben
- Deutsche Forschungsgemeinschaft (DFG)
FZT 111 Zentrum für Regenerative Therapien Dresden (CRTD)
ID: 22137416 - Deutsche Forschungsgemeinschaft (DFG)
EXC 168
Zentrum für Regenerative Therapien Dresden
(CRTD)
ID: 32725986 - Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:14-qucosa2-995940
- Veröffentlichungsdatum Qucosa
- 04.08.2026
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY 4.0