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The Signal Peptide Of The Amyloid Precursor Protein Forms Amyloid-Like Aggregates And Enhances Aβ42 Aggregation, Kundlik Gadhave, Taniya Bhardwaj, Vladimir N. Uversky, Michele Vendruscolo, Rajanish Giri

Molecular Medicine Faculty Publications

Signal sequences are short peptides at the N terminus of proteins destined for the secretion pathway. Typically, after cleavage by peptidases, signal peptides are degraded by intra-membrane proteases. In some cases, however, signal peptides can be processed further and released into the endoplasmic reticulum, secretion pathways, or cytoplasm. The consequences of these processes remain unclear, in particular considering that dysregulated signal peptides could potentially aggregate and induce cytotoxicity. To investigate this problem, we study the signal peptide of the amyloid precursor protein (APP), which originates the Alzheimer’s β-amyloid (Aβ) peptide. Our results show that this signal peptide (residues 1–17 of …