Identification of prion protein-derived peptides of potential use in Alzheimer's disease therapy

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1864

Article

Nieznanska, Hanna¹  Bandyszewska, Magdalena¹  Surewicz, Krystyna²  Zajkowski, Tomasz³  Surewicz, Witold K.²  Nieznanski, Krzysztof¹ 

[1] Polish Acad Sci, Nencki Inst Expt Biol, Dept Biochem, 3 Pasteur Str, PL-02093 Warsaw, Poland

[2] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA

[3] Univ Warsaw, Ctr New Technol, Lab Mol Neurobiol, PL-02097 Warsaw, Poland

关键词: Prion protein;    A beta peptide;    Alzheimer's disease;    Amyloid;    Neurotoxicity;   

DOI  :  10.1016/j.bbadis.2018.03.023

来源: Elsevier

【 摘 要 】

Soluble form of the prion protein (PrP) has been previously shown to interact with amyloid-beta (A beta) peptides, suppressing their fibrillization as well as toxicity, which indicates that this protein may play a protective role in Alzheimer's disease (AD). The shortest known PrP fragment retaining all of these properties corresponds to physiologically generated proteolytic polypeptide PrP23-110/111, called N1. Here we have identified two N1 derived synthetic peptides, encompassing residues 23-50 (PrP23-50) and 90-112 (PrP90-112), which bind to A beta 1-42 protofibrillar oligomers as well as amyloid fibrils. We found that, akin to N1, the abovementioned synthetic peptides not only reduce the initial rate of A beta fibrillization, but also alter the aggregation pathway of A beta, inhibiting formation of protofibrillar oligomers and facilitating amorphous aggregation. Furthermore, our data show that N1, PrP23-50 and PrP90-112 protect cultured hippocampal neurons from neurotoxic effects of A beta oligomers, preventing oligomers-induced retraction of neurites and loss of cell membrane integrity. The above PrP fragments can also attenuate neuronal intake of A beta. Our results strongly suggest that synthetic peptides such as PrP23-50 and PrP90-112 can be useful in designing a novel class of therapeutics in AD.

【 授权许可】

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