ArticleScientific reports2021
Toxicity of internalized polyalanine to cells depends on aggregation.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- DRED: A Comprehensive Database of Genes Related to Repeat Expansion Diseases.Genomics, proteomics & bioinformatics · 2024Article
- Inner and outer penetrating spinal cord injuries lead to distinct overground walking in mice.IBRO neuroscience reports · 2024Article
- Alternative low-populated conformations prompt phase transitions in polyalanine repeat expansions.Nature communications · 2024Article
- Non-fibril form but not fibril form of human islet amyloid polypeptide 8-20 changes brain functions in mice.PloS one · 2024Article
- Mitochondrial Dysfunction in Repeat Expansion Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Article
- Conditioned medium from BV2 microglial cells having polyleucine specifically alters startle response in mice.Scientific reports · 2022Article
- Exogenous polyserine and polyleucine are toxic to recipient cells.Scientific reports · 2022Article
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Authors and funding
6 authors.
Funding
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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.
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