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Perez-Garmendia R, Gevorkian G. Pyroglutamate-Modified Amyloid Beta Peptides: Emerging Targets for Alzheimer´s Disease Immunotherapy. Curr Neuropharmacol. 2013;11(5):491-8doi: 10.2174/1570159X11311050004.
Perez-Garmendia, R., & Gevorkian, G. (2013). Pyroglutamate-Modified Amyloid Beta Peptides: Emerging Targets for Alzheimer´s Disease Immunotherapy. Current neuropharmacology, 11(5), 491-8. https://doi.org/10.2174/1570159X11311050004
Perez-Garmendia, Roxanna, and Gevorkian, Goar. "Pyroglutamate-Modified Amyloid Beta Peptides: Emerging Targets for Alzheimer´s Disease Immunotherapy." Current neuropharmacology vol. 11,5 (2013): 491-8. doi: https://doi.org/10.2174/1570159X11311050004
Perez-Garmendia R, Gevorkian G. Pyroglutamate-Modified Amyloid Beta Peptides: Emerging Targets for Alzheimer´s Disease Immunotherapy. Curr Neuropharmacol. 2013 Sep;11(5):491-8. doi: 10.2174/1570159X11311050004. PMID: 24403873; PMCID: PMC3763757.
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Curr Neuropharmacol. 2013 Sep;11(5):491-8. doi: 10.2174/1570159X11311050004.

Pyroglutamate-Modified Amyloid Beta Peptides: Emerging Targets for Alzheimer´s Disease Immunotherapy.

Current neuropharmacology

Roxanna Perez-Garmendia, Goar Gevorkian

Affiliations

  1. Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Mexico DF, Mexico.

PMID: 24403873 PMCID: PMC3763757 DOI: 10.2174/1570159X11311050004

Abstract

Extracellular and intraneuronal accumulation of amyloid-beta (Aβ) peptide aggregates in the brain has been hypothesized to play an important role in the neuropathology of Alzheimer's Disease (AD). The main Aβ variants detected in the human brain are Aβ1-40 and Aβ1-42, however a significant proportion of AD brain Aβ consists also of N-terminal truncated species. Pyroglutamate-modified Aβ peptides have been demonstrated to be the predominant components among all N-terminal truncated Aβ species in AD brains and represent highly desirable and abundant therapeutic targets. The current review describes the properties and localization of two pyroglutamate-modified Aβ peptides, AβN3(pE) and AβN11(pE), in the brain. The role of glutaminyl cyclase (QC) in the formation of these peptides is also addressed. In addition, two potential therapeutic strategies, the inhibition of QC and immunotherapy approaches, and clinical trials aimed to target these important pathological Aβ species are reviewed.

Keywords: Alzheimer´s disease; N-terminal truncated amyloid beta; amyloid-beta; glutaminyl cyclase; immunotherapy; pyroglutamate-modified amyloid-beta.

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