論文 - 詳細
| RRC ID | 88986 |
|---|---|
| 著者 | Ngana GS, Di Bernardo MA, Surette MG, MacNeil LT. |
| タイトル | Actinomyces viscosus promotes neuroprotection in C. elegans models of Parkinson's disease. |
| ジャーナル | Mech Ageing Dev |
| Abstract |
Parkinson's Disease is characterized by selective degeneration of dopaminergic neurons, primarily in the substantia nigra pars compacta, as well as accumulation of alpha-synuclein enriched protein aggregates within neurons. The pathogenesis of PD is still not completely understood, and no treatments exist that alter disease progression. Obvious genetic causes are detected in only a small number of PD patients (5-10 %), suggesting that environmental factors play a significant role the development of PD. Correlative studies suggest that the microbiota could be an important environmental modifier of neurodegeneration. We identified a microbiotal isolate, Actinomyces viscosus, that reduced neurodegeneration in C. elegans expressing a pathological mutant form (G2019S) of leucine-rich repeat kinase 2 (LRRK2) in dopaminergic neurons. A. viscosus also suppressed autophagic dysfunction in these animals and reduced alpha-synuclein aggregation in a synucleinopathy model. Global gene expression analysis revealed increased expression of aspartic cathepsins in response to A. viscosus. Consistent with the involvement of these proteins in neuroprotection, we found that reducing aspartic cathepsin function increased neurodegeneration in the LRRK2 transgenic model. Our findings contribute to the current understanding of how the gut microbiota may influence PD, elucidating one potential mechanism of microbiota-mediated neuroprotection. |
| 巻・号 | 225 |
| ページ | 112061 |
| 公開日 | 2025-6-1 |
| DOI | 10.1016/j.mad.2025.112061 |
| PII | S0047-6374(25)00037-5 |
| PMID | 40258426 |
| MeSH | Actinomyces* Animals Animals, Genetically Modified Autophagy Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans* / microbiology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Disease Models, Animal Dopaminergic Neurons* / metabolism Dopaminergic Neurons* / pathology Humans Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism Neuroprotection* Parkinson Disease* / genetics Parkinson Disease* / metabolism Parkinson Disease* / microbiology Parkinson Disease* / pathology alpha-Synuclein / genetics alpha-Synuclein / metabolism |
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オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 一般微生物 | JCM12987 JCM8349 JCM16131 JCM8353 JCM15918 |