Neutralization of IL-17 rescues amyloid-β-induced neuroinflammation and memory impairment
Research output: Contribution to journal › Article
Colleges, School and Institutes
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy.
- Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR, 80131, Naples, Italy.
Background and purpose: Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state, and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of Th17 cells in the pathogenesis of AD-related neuroinflammation has been reported in several studies. However, the role of the cytokine, IL-17 has not been well addressed. Herein, we investigate the effects of IL-17 neutralizing antibody (IL-17Ab) injected by i.c.v. or intranasal (IN) routes on amyloid-β (Aβ)-induced neuroinflammation and memory impairment in mice. Experimental approach: Aβ 1–42 was injected into cerebral ventricles of adult CD1 mice. These mice received IL-17Ab via i.c.v. either at 1 h prior to Aβ 1–42 injection or IN 5 and 12 days after Aβ 1–42 injection. After 7 and 14 days of Aβ 1–42 administration, we evaluated olfactory, spatial and working memory and performed biochemical analyses on whole brain and specific brain areas. Key results: Pretreatment with IL-17Ab, given, i.c.v., markedly reduced Aβ 1–42-induced neurodegeneration, improved memory function, and prevented the increase of pro-inflammatory mediators in a dose-dependent manner at 7 and 14 days. Similarly, the double IN administration of IL-17Ab after Aβ 1–42 injection reduced neurodegeneration, memory decline, and the levels of proinflammatory mediators and cytokines. Conclusion and implications: These findings suggest that the IL-17Ab reduced neuroinflammation and behavioural symptoms induced by Aβ. The efficacy of IL-17Ab IN administration in reducing Aβ 1–42 neurodegeneration points to a possible future therapeutic approach in patients with AD. Linked Articles: This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.
|Number of pages||14|
|Journal||British Journal of Pharmacology|
|Early online date||23 Jan 2019|
|Publication status||Published - Sep 2019|
- Alzheimer, immunotherapy, intranasal, IL-17, neuroinflammation