ALS-linked mutant SOD1 proteins promote A β aggregates in ALS through direct interaction with Aβ.

In this study, we have demonstrated that the Aβ-binding region is exposed on the SOD1 surface through the conformational changes due to misfolding of SOD1. Interestingly, we found that the intracellular aggregation of Aβ is enhanced through the direct interaction of Aβ with the Aβ-binding region exposed to misfolded SOD1. Ultimately, increased Aβ aggregation by this interaction promotes neuronal cell death. Consistent with this result, Aβ aggregates was three-fold higher in the brains of G93A transgenic mice than those of non Tg. Our study provides the first direct evidence that Aβ, an AD-linked factor, is associated to the pathogenesis of ALS and provides molecular clues to understand common aggregation mechanisms in the pathogenesis of neurodegenerative diseases. Furthermore, it will provide new insights into the development of therapeutic approaches for ALS.
PMID: 28864422 [PubMed - indexed for MEDLINE]

Source: Biochemical and Biophysical Research communications - October 18, 2017 Category: Biochemistry Authors: Jang JY, Cho H, Park HY, Rhim H, Kang S Tags: Biochem Biophys Res Commun Source Type: research