The β amyloid peptide can act as a modular aggregation domain

NEUROBIOLOGY OF DISEASE

卷:32

Article

Link, Christopher D.¹  Fonte, Virginia¹  Roberts, Christine M.¹  Hiester, Brian¹  Silverman, Michael A.² 

[1] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA

[2] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada

关键词: Alzheimer's disease;    C. elegans;    Transgenic;    Neurodegeneration;    gamma-secretase;    alpha-secretase;    AlCD;   

DOI  :  10.1016/j.nbd.2008.08.003

来源: Elsevier

【 摘 要 】

Although there is compelling evidence that the beta amyloid peptide (A beta) 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 A beta 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 (Leu(17) to Pro) in the beta peptide sequence can abolish this cis capacity to induce aggregation. Introduction of this substitution into full-length APP (i.e., a Leu(613)Pro 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. (C) 2008 Elsevier Inc. All rights reserved.

【 授权许可】

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