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

Author(s): Roxanna Perez-Garmendia, Goar Gevorkian

Journal Name: Current Neuropharmacology

Volume 11 , Issue 5 , 2013

Become EABM
Become Reviewer


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 Nterminal 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, amyloid-beta, glutaminyl cyclase, immunotherapy, N-terminal truncated amyloid beta, pyroglutamate-modified amyloid-beta.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2013
Page: [491 - 498]
Pages: 8
DOI: 10.2174/1570159X11311050004
Price: $65

Article Metrics

PDF: 11