論文 - 詳細
| RRC ID | 83318 |
|---|---|
| 著者 | Jiang M, Ge Z, Yin S, Liu Y, Gao H, Lu L, Wang H, Li C, Ni J, Pan Y, Lin L. |
| タイトル | Cathepsin B Modulates Alzheimer's Disease Pathology Through SAPK/JNK Signals Following Administration of Porphyromonas gingivalis-Derived Outer Membrane Vesicles. |
| ジャーナル | J Clin Periodontol |
| Abstract |
AIM:Porphyromonas gingivalis , a consensus periodontal pathogen, is thought to be involved in Alzheimer's disease (AD) progression, and P. gingivalis -derived outer membrane vesicles (PgOMVs) are a key toxic factor in inducing AD pathology. This study aimed to clarify the regulatory mechanism underlying the PgOMV-induced AD-like phenotype. MATERIALS AND METHODS:We intraperitoneally injected PgOMVs into the periphery of wild-type and CatB knockout mice for 4 or 8 weeks to assess the effect of CatB on PgOMV-induced AD pathology. Mice were evaluated for cognitive change, tau phosphorylation, microglial activation, neuroinflammation and synapse loss. Microglial and primary neuron culture were prepared to verify the in vivo results. RESULTS:CatB deficiency significantly alleviated PgOMV-induced cognitive dysfunction, microglia-mediated neuroinflammation, tau hyperphosphorylation and synapse loss. Subsequent transcriptomic analysis, immunofluorescence and immunoblotting suggested that CatB modulates microglia-mediated neuroinflammation through stress-activated protein kinases (SAPK)/Jun amino-terminal kinases (JNK) signals after administration of PgOMVs, which in turn regulates neuronal tau phosphorylation and synapse loss in a SAPK/JNK-dependent manner. CONCLUSION:Our study unveils a previously unknown role of CatB in regulating PgOMV-induced AD pathology. |
| 巻・号 | 52(3) |
| ページ | 434-456 |
| 公開日 | 2025-3-1 |
| DOI | 10.1111/jcpe.14109 |
| PMID | 39726227 |
| MeSH | Alzheimer Disease* Animals Bacterial Outer Membrane / metabolism Cathepsin B* / metabolism Disease Models, Animal MAP Kinase Signaling System Male Mice Mice, Inbred C57BL Mice, Knockout* Microglia / metabolism Phosphorylation Porphyromonas gingivalis* tau Proteins / metabolism |
| IF | 5.241 |
| リソース情報 | |
| ヒト・動物細胞 | MG6(RCB2403) |