Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges

被引：40

作者：

Cynis, Holger ^{[1
,2
]}

Frost, Jeffrey L. ^{[1
,3
]}

Crehan, Helen ^{[1
]}

Lemere, Cynthia A. ^{[1
]}

机构：

[1] Harvard Med Sch, Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, 77 Ave Louis Pasteur,NRB636, Boston, MA 02115 USA

[2] Fraunhofer Inst Cell Therapy & Immunol, Weinbergweg 22, D-06120 Halle, Germany

[3] Univ Massachusetts, Sch Med, 55 Lake Ave North, Worcester, MA 01605 USA

来源：

MOLECULAR NEURODEGENERATION | 2016年 / 11卷

基金：

美国国家卫生研究院;

关键词：

Amyloid-beta; Pyroglutamate-3 A beta; Immunotherapy; Vaccine; Glutaminyl cyclases; AMYLOID PRECURSOR PROTEIN; TRANSGENIC MOUSE MODEL; MODERATE ALZHEIMERS-DISEASE; PRESENILIN-1; MUTATION; GLUTAMINYL CYCLASES; GAMMA-SECRETASE; PEPTIDE; DEPOSITION; MICE; IMMUNIZATION;

D O I：

10.1186/s13024-016-0115-2

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Immunization against amyloid-beta (A beta) peptides deposited in Alzheimer's disease (AD) has shown considerable therapeutic effect in animal models however, the translation into human Alzheimer's patients is challenging. In recent years, a number of promising A beta immunotherapy trials failed to reach primary study endpoints. Aside from uncertainties in the selection of patients and the start and duration of treatment, these results also suggest that the mechanisms underlying AD are still not fully understood. Thorough characterizations of protein aggregates in AD brain have revealed a conspicuous heterogeneity of A beta peptides enabling the study of the toxic potential of each of the major forms. One such form, amino-terminally truncated and modified pyroglutamate (pGlu)-3 A beta peptide appears to play a seminal role for disease initiation, qualifying it as novel target for immunotherapy approaches.

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页数：11

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