| Autor: |
Hitomi Komura, Shota Kakio, Tomoya Sasahara, Yoshie Arai, Naomi Takino, Michio Sato, Kaori Satomura, Takayuki Ohnishi, Yo-ichi Nabeshima, Shin-ichi Muramatsu, Isao Kii, Minako Hoshi |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 13, Iss , Pp 452-477 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2019.01.018 |
| Popis: |
Summary: We identified ∼30-mer amyloid-β protein (Aβ) assemblies, termed amylospheroids, from brains of patients with Alzheimer disease (AD) as toxic entities responsible for neurodegeneration and showed that Na+,K+-ATPase α3 (NAKα3) is the sole target of amylospheroid-mediated neurodegeneration. However, it remains unclear where in neurons amylospheroids form and how they reach their targets to induce neurodegeneration. Here, we present an in vitro culture system designed to chronologically follow amylospheroid formation in mature neurons expressing amyloid precursor protein bearing early-onset AD mutations. Amylospheroids were found to accumulate mainly in the trans-Golgi network of excitatory neurons and were initially transported in axons. Proteasome inhibition dramatically increased amylospheroid amounts in trans-Golgi by increasing Aβ levels and induced dendritic transport. Amylospheroids were secreted and caused the degeneration of adjacent NAKα3-expressing neurons. Interestingly, the ASPD-producing neurons later died non-apoptotically. Our findings demonstrate a link between ASPD levels and proteasome function, which may have important implications for AD pathophysiology. : Pathophysiology; Neuroscience; Cellular Neuroscience Subject Areas: Pathophysiology, Neuroscience, Cellular Neuroscience |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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