RRC ID 68966
Author Iizuka Y, Owada R, Kawasaki T, Hayashi F, Sonoyama M, Nakamura K.
Title Toxicity of internalized polyalanine to cells depends on aggregation.
Journal 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.
Volume 11(1)
Pages 23441
Published 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
Human and Animal Cells PC-12(RCB0009)