The β amyloid peptide can act as a modular aggregation domain

Neurobiology of Disease

Virginia Fonte¹  Gretchen H. Stein²  Michael A. Silverman³  Christine M. Roberts³  Brian Hiester³  Christopher D. Link³ 

[1] Corresponding author. Fax: [phone].;Biological Sciences, Simon Fraser University, Burnaby, Canada BC V5A 1S6;Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA;

关键词: Alzheimer's disease;    C. elegans;    Transgenic;    Neurodegeneration;    γ-secretase;    α-secretase;   

DOI  :  

来源: DOAJ

【 摘 要 】

Although there is compelling evidence that the β amyloid peptide (Aβ) can be centrally involved in Alzheimer's disease, the natural role (if any) of this peptide remains unclear. Here we use green fluorescent protein (GFP) fusions to demonstrate that the Aβ sequence, like prion domains, can act as a modular aggregation domain when terminally appended to a normally soluble protein. We find that a single amino acid substitution (Leu17 to Pro) in the β peptide sequence can abolish this cis capacity to induce aggregation. Introduction of this substitution into full-length APP (i.e., a Leu613Pro substitution in APP695) alters the processing of APP leading to the accumulation of the C99 C-terminal fragment (CTF). We suggest that in at least some aggregation disease-related proteins the presence of an aggregation domain is not “accidental”, but reflects a selected role of these domains in modulating the trafficking or metabolism of the parental protein.

【 授权许可】

Unknown