Pathobiology of the autophagy-lysosomal pathway in the Huntington’s disease brain
The findings collectively suggest that upregulated lysosomal biogenesis and preserved proteolysis maintain autophagic clearance in early-stage HD, but the observed progressive HTT build-up and AL accumulation at advanced disease stages may signify a failure in autophagy substrate clearance. These findings support the prospect that ALP stimulation applied at early disease stages, when clearance machinery is fully competent, could lead to therapeutic benefits in HD patients.
Authors
- Dun‐Sheng Yang (ORCID: https://orcid.org/0000-0001-9259-3015)
- Ralph A. Nixon (ORCID: https://orcid.org/0000-0001-5124-1021)
- Veeranna
- Sandipkumar Darji (ORCID: https://orcid.org/0000-0003-4197-4971)
- Philip Stavrides (ORCID: https://orcid.org/0000-0003-1225-3577)
- Martin J. Berg (ORCID: https://orcid.org/0000-0002-7353-8851)
- Deanna M. Marchionini (ORCID: https://orcid.org/0000-0003-2071-1064)
- Panaiyur S. Mohan
- Asok Kumar
- Corrinne M. Rosa
Institutions
- Nathan Kline Institute for Psychiatric Research (US)
- CHDI Foundation (US)
- New York University (US)
Publication Details
- Journal
- Acta Neuropathologica Communications
- Published
- 2025-11-07
- DOI
- https://doi.org/10.1186/s40478-025-02131-8
- Citations
- 1
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 1.35
Funders
- CHDI Foundation
- Emory University