論文 - 詳細
| RRC ID | 84045 |
|---|---|
| 著者 | Foster SG, Mathew S, Labarre A, Parker JA, Tompkins TA, Binda S. |
| タイトル | Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179 Prolong Lifespan and Mitigate Amyloid-β Toxicity in C. elegans via Distinct Mechanisms. |
| ジャーナル | J Alzheimers Dis |
| Abstract |
BACKGROUND:Recent advances linking gut dysbiosis with neurocognitive disorders such as Alzheimer's disease (AD) suggest that the microbiota-gut-brain axis could be targeted for AD prevention, management, or treatment. OBJECTIVE:We sought to identify probiotics that can delay Aβ-induced paralysis. METHODS:Using C. elegans expressing human amyloid-β (Aβ)1-42 in body wall muscles (GMC101), we assessed the effects of several probiotic strains on paralysis. RESULTS:We found that Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179, but not their supernatants or heat-treated forms, delayed paralysis and prolonged lifespan without affecting the levels of amyloid-β aggregates. To uncover the mechanism involved, we explored the role of two known pathways involved in neurogenerative diseases, namely mitophagy, via deletion of the mitophagy factor PINK-1, and fatty acid desaturation, via deletion of the Δ9 desaturase FAT-5. Pink-1 deletion in GMC101 worms did not modify the life-prolonging and anti-paralysis effects of HA-114 but reduced the protective effect of R0179 against paralysis without affecting its life-prolonging effect. Upon fat5 deletion in GMC101 worms, the monounsaturated C14:1 and C16:1 FAs conserved their beneficial effect while the saturated C14:0 and C16:0 FAs did not. The beneficial effects of R0179 on both lifespan and paralysis remained unaffected by fat-5 deletion, while the beneficial effect of HA-114 on paralysis and lifespan was significantly reduced. CONCLUSIONS:Collectively with clinical and preclinical evidence in other models, our results suggest that HA-114 or R0179 could be studied as potential therapeutical adjuncts in neurodegenerative diseases such as AD. |
| 巻・号 | 101(1) |
| ページ | 49-60 |
| 公開日 | 2024-1-1 |
| DOI | 10.3233/JAD-230948 |
| PII | JAD230948 |
| PMID | 39093068 |
| PMC | PMC11380293 |
| MeSH | Amyloid beta-Peptides* / metabolism Amyloid beta-Peptides* / toxicity Animals Animals, Genetically Modified Bacillus subtilis* Caenorhabditis elegans* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Humans Lacticaseibacillus rhamnosus* Longevity* / drug effects Paralysis Peptide Fragments / metabolism Peptide Fragments / toxicity Probiotics* |
| リソース情報 | |
| 線虫 | tm420 |