Discovery of Autophagy Modulators that Increase I1061T NPC1 Expression and Promote Cholesterol Efflux in Niemann-Pick Type C Patient-Derived Fibroblasts
may serve as a proteostasis modulator or small-molecule chaperone that upregulates autophagy to a level that is predominantly cytoprotective and increases the proportion of properly folded mutant NPC1, thus increasing NPC1 expression levels and alleviating cholesterol accumulation and associated phenotypes. This work, along with future mechanistic studies, contributes to the development of novel strategies to modulate autophagy and proteostasis with potentially broad therapeutic applications.
Authors
- Leslie N. Aldrich (ORCID: https://orcid.org/0000-0001-8406-720X)
- Zoe A. Petros
- Thu T. A. Nguyen (ORCID: https://orcid.org/0000-0001-8617-3305)
- Qiwen Gao (ORCID: https://orcid.org/0000-0001-5043-9669)
- Judith Storch (ORCID: https://orcid.org/0000-0001-5482-1777)
- Maryna Salkovski
- Erica M. Gerlach
- Ryan S. Hippman (ORCID: https://orcid.org/0000-0002-5283-5902)
- Melissa A. Korkmaz (ORCID: https://orcid.org/0000-0003-4234-8702)
- Olga V. Ilnytska
- Stephanie M. Cologna (ORCID: https://orcid.org/0000-0002-3541-3361)
- Yaneris M Alvarado-Cartagena
- Andrea Arrieche Suarez
- Ivan Pavlinov
Institutions
- University of Illinois Chicago (US)
- Rutgers Sexual and Reproductive Health and Rights (NL)
- Frederick National Laboratory for Cancer Research (US)
- National Cancer Institute (US)
Publication Details
- Journal
- ACS Chemical Biology
- Published
- 2026-04-03
- DOI
- https://doi.org/10.1021/acschembio.6c00039
- Primary Topic
- Lysosomal Storage Disorders Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ara Parseghian Medical Research Fund
- National Institute of Neurological Disorders and Stroke
- Basic Research Laboratory