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

作者：Perez Garmendia Roxanna; Gevorkian Goar^*

来源：Current Neuropharmacology, 2013, 11(5): 491-498.

• Alzheimer's disease
• amyloid-beta
• glutaminyl cyclase
• immunotherapy
• N-terminal truncated amyloid beta
• pyroglutamate-modified amyloid-beta

Extracellular and intraneuronal accumulation of amyloid-beta (A beta) peptide aggregates in the brain has been hypothesized to play an important role in the neuropathology of Alzheimer's Disease (AD). The main A beta variants detected in the human brain are A beta 1-40 and A beta 1-42, however a significant proportion of AD brain A beta consists also of N-terminal truncated species. Pyroglutamate-modified A beta peptides have been demonstrated to be the predominant components among all N-terminal truncated A beta species in AD brains and represent highly desirable and abundant therapeutic targets. The current review describes the properties and localization of two pyroglutamate-modified A beta peptides, A beta N3(pE) and A beta N11(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 A beta species are reviewed.

• 出版日期2013-9