論文 - 詳細
| RRC ID | 57088 |
|---|---|
| 著者 | Maksoud E, Liao EH, Haghighi AP. |
| タイトル | A Neuron-Glial Trans-Signaling Cascade Mediates LRRK2-Induced Neurodegeneration. |
| ジャーナル | Cell Rep |
| Abstract |
Pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2) induce an age-dependent loss of dopaminergic (DA) neurons. We have identified Furin 1, a pro-protein convertase, as a translational target of LRRK2 in DA neurons. Transgenic knockdown of Furin1 or its substrate the bone morphogenic protein (BMP) ligand glass bottom boat (Gbb) protects against LRRK2-induced loss of DA neurons. LRRK2 enhances the accumulation of phosphorylated Mad (pMad) in the nuclei of glial cells in the vicinity of DA neurons but not in DA neurons. Consistently, exposure to paraquat enhances Furin 1 levels in DA neurons and induces BMP signaling in glia. In support of a neuron-glial signaling model, knocking down BMP pathway members only in glia, but not in neurons, can protect against paraquat toxicity. We propose that a neuron-glial BMP-signaling cascade is critical for mediating age-dependent neurodegeneration in two models of Parkinson's disease, thus opening avenues for future therapeutic interventions. |
| 巻・号 | 26(7) |
| ページ | 1774-1786.e4 |
| 公開日 | 2019-2-12 |
| DOI | 10.1016/j.celrep.2019.01.077 |
| PII | S2211-1247(19)30106-8 |
| PMID | 30759389 |
| PMC | PMC6474846 |
| MeSH | Humans Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics* Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism Neurodegenerative Diseases / genetics* Neuroglia / metabolism* Signal Transduction |
| IF | 7.815 |
| 引用数 | 3 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 23 |
| 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 | |
| ショウジョウバエ | DGRC#105666 |