論文 - 詳細
| RRC ID | 83817 |
|---|---|
| 著者 | Guillaud L, Garanzini A, Zakhia S, De la Fuente S, Dimitrov D, Boerner S, Terenzio M. |
| タイトル | Loss of intracellular ATP affects axoplasmic viscosity and pathological protein aggregation in mammalian neurons. |
| ジャーナル | Sci Adv |
| Abstract |
Neurodegenerative diseases display synaptic deficits, mitochondrial defects, and protein aggregation. We show that intracellular adenosine triphosphate (ATP) regulates axoplasmic viscosity and protein aggregation in mammalian neurons. Decreased intracellular ATP upon mitochondrial inhibition leads to axoterminal cytosol, synaptic vesicles, and active zone component condensation, modulating the functional organization of mouse glutamatergic synapses. Proteins involved in the pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) condensed and underwent ATP-dependent liquid phase separation in vitro. Human inducible pluripotent stem cell-derived neurons from patients with PD and ALS displayed reduced axoplasmic fluidity and decreased intracellular ATP. Last, nicotinamide mononucleotide treatment successfully rescued intracellular ATP levels and axoplasmic viscosity in neurons from patients with PD and ALS and reduced TAR DNA-binding protein 43 (TDP-43) aggregation in human motor neurons derived from a patient with ALS. Thus, our data suggest that the hydrotropic activity of ATP contributes to the regulation of neuronal homeostasis under both physiological and pathological conditions. |
| 巻・号 | 11(17) |
| ページ | eadq6077 |
| 公開日 | 2025-4-25 |
| DOI | 10.1126/sciadv.adq6077 |
| PMID | 40267187 |
| PMC | PMC12017319 |
| MeSH | Adenosine Triphosphate* / metabolism Alzheimer Disease / metabolism Alzheimer Disease / pathology Amyotrophic Lateral Sclerosis / metabolism Amyotrophic Lateral Sclerosis / pathology Animals Axons* / metabolism DNA-Binding Proteins / metabolism Humans Induced Pluripotent Stem Cells / metabolism Mice Mitochondria / metabolism Neurons* / metabolism Parkinson Disease / metabolism Parkinson Disease / pathology Protein Aggregates Protein Aggregation, Pathological* / metabolism Protein Aggregation, Pathological* / pathology Viscosity |
| IF | 13.117 |
| 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 | Bluesky |
| 各媒体での言及数の合計 | 69 |
| 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 | |
| ヒト・動物細胞 | HPS0097(HPS0097) 454E2(HPS0077) |