RAB5 Hyperactivation Induces APP‐Driven Endolysosomal and Autophagic Dysfunction in Down Syndrome: Reversal by Antisense Oligonucleotides Targeting <i>App</i> and <i>Rab5</i>
Our results demonstrate that APP dose-driven RAB5 hyperactivation disrupts endosomal Rab cascades, endosome maturation, and autophagy function in DS. Targeting either APP or Rab5 may offer promising therapeutic strategies to restore cellular function and mitigate DS-AD pathologies.
Authors
- Xinxin Zuo
- William C. Mobley (ORCID: https://orcid.org/0000-0002-6408-9548)
- Xu‐Qiao Chen (ORCID: https://orcid.org/0000-0001-9799-7246)
- Hien Zhao (ORCID: https://orcid.org/0009-0000-0904-8201)
Institutions
- Ionis Pharmaceuticals (United States) (US)
- University of California San Diego (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/alz70855_102499
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00