Document Type
Article
Publication Date
5-18-2024
Original Citation
Hull B,
Miller K,
Corban C,
Backer G,
Sheehan S,
Korstanje R,
Sutphin GL.
3-Hydroxyanthranilic Acid Delays Paralysis in Biomolecules. 2024;14(5).
Keywords
JMG, Caenorhabditis elegans, Animals, Amyloid beta-Peptides, Peptides, 3-Hydroxyanthranilic Acid, Paralysis, Disease Models, Animal, Alzheimer Disease, Caenorhabditis elegans Proteins, Huntington Disease, Dioxygenases
JAX Source
Biomolecules. 2024;14(5).
ISSN
2218-273X
PMID
38786006
DOI
https://doi.org/10.3390/biom14050599
Grant
This research was funded by the National Institute on Aging grant P30AG038070, and The Jackson Laboratory and National Institute on Aging grant R35GM133588 to G.L.S.
Abstract
Age is the primary risk factor for neurodegenerative diseases such as Alzheimer’s and Huntington’s disease. Alzheimer’s disease is the most common form of dementia and a leading cause of death in the elderly population of the United States. No effective treatments for these diseases currently exist. Identifying effective treatments for Alzheimer’s, Huntington’s, and other neurodegenerative diseases is a major current focus of national scientific resources, and there is a critical need for novel therapeutic strategies. Here, we investigate the potential for targeting the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) using Caenorhabditis elegans expressing amyloid-beta or a polyglutamine peptide in body wall muscle, modeling the proteotoxicity in Alzheimer’s and Huntington’s disease, respectively. We show that knocking down the enzyme that degrades 3HAA, 3HAA dioxygenase (HAAO), delays the age-associated paralysis in both models. This effect on paralysis was independent of the protein aggregation in the polyglutamine model. We also show that the mechanism of protection against proteotoxicity from HAAO knockdown is mimicked by 3HAA supplementation, supporting elevated 3HAA as the mediating event linking HAAO knockdown to delayed paralysis. This work demonstrates the potential for 3HAA as a targeted therapeutic in neurodegenerative disease, though the mechanism is yet to be explored.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.