| RRC ID |
68966
|
| 著者 |
Iizuka Y, Owada R, Kawasaki T, Hayashi F, Sonoyama M, Nakamura K.
|
| タイトル |
Toxicity of internalized polyalanine to cells depends on aggregation.
|
| ジャーナル |
Sci Rep
|
| Abstract |
In polyalanine (PA) diseases, the disease-causing transcription factors contain an expansion of alanine repeats. While aggregated proteins that are responsible for the pathogenesis of neurodegenerative disorders show cell-to-cell propagation and thereby exert toxic effects on the recipient cells, whether this is also the case with expanded PA has not been studied. It is also not known whether the internalized PA is toxic to recipient cells based on the degree of aggregation. In this study, we therefore prepared different degrees of aggregation of a peptide having 13 alanine repeats without flanking sequences of PA disease-causative proteins (13A). The aggregated 13A was spontaneously taken up by neuron-like cultured cells. Functionally, strong aggregates but not weak aggregates displayed a deficit in neuron-like differentiation in vitro. Moreover, the injection of strong but not weak 13A aggregates into the ventricle of mice during the neonatal stage led to enhanced spontaneous motor activity later in life. Thus, PA in the extracellular space has the potential to enter adjacent cells, and may exert toxicity depending on the degree of aggregation.
|
| 巻・号 |
11(1)
|
| ページ |
23441
|
| 公開日 |
2021-12-6
|
| DOI |
10.1038/s41598-021-02889-6
|
| PII |
10.1038/s41598-021-02889-6
|
| PMID |
34873226
|
| PMC |
PMC8648788
|
| MeSH |
Alanine / chemistry*
Animals
Behavior, Animal
Brain / drug effects*
Extracellular Space
Mice
Mice, Inbred ICR
Microscopy, Electron, Transmission
Motor Skills
Neurosciences
PC12 Cells
Peptides / chemistry*
Protein Structure, Secondary
Rats
Transcription Factors / metabolism
Transcription, Genetic
Transcriptional Activation
Trinucleotide Repeat Expansion
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
PC-12(RCB0009) |
