Carnosine Counteracts the Molecular Alterations Aβ Oligomers-Induced in Human Retinal Pigment Epithelial Cells

Author:

Caruso Giuseppe12ORCID,Fresta Claudia G.1,Fidilio Annamaria2ORCID,Lazzara Francesca3ORCID,Musso Nicolò34ORCID,Cardaci Vincenzo56ORCID,Drago Filippo3,Caraci Filippo12,Bucolo Claudio37

Affiliation:

1. Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy

2. Unit of Neuropharmacology and Translational Neurosciences, Oasi Research Institute-IRCCS, 94018 Troina, Italy

3. Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy

4. Bio-Nanotech Research and Innovation Tower (BRIT), University of Catania, 95123 Catania, Italy

5. Vita-Salute San Raffaele University, 20132 Milano, Italy

6. Scuola Superiore di Catania, University of Catania, 95123 Catania, Italy

7. Center for Research in Ocular Pharmacology-CERFO, University of Catania, 95123 Catania, Italy

Abstract

Age-related macular degeneration (AMD) has been described as a progressive eye disease characterized by irreversible impairment of central vision, and unfortunately, an effective treatment is still not available. It is well-known that amyloid-beta (Aβ) peptide is one of the major culprits in causing neurodegeneration in Alzheimer’s disease (AD). The extracellular accumulation of this peptide has also been found in drusen which lies under the retinal pigment epithelium (RPE) and represents one of the early signs of AMD pathology. Aβ aggregates, especially in the form of oligomers, are able to induce pro-oxidant (oxidative stress) and pro-inflammatory phenomena in RPE cells. ARPE-19 is a spontaneously arising human RPE cell line validated for drug discovery processes in AMD. In the present study, we employed ARPE-19 treated with Aβ oligomers, representing an in vitro model of AMD. We used a combination of methods, including ATPlite, quantitative real-time PCR, immunocytochemistry, as well as a fluorescent probe for reactive oxygen species to investigate the molecular alterations induced by Aβ oligomers. In particular, we found that Aβ exposure decreased the cell viability of ARPE-19 cells which was paralleled by increased inflammation (increased expression of pro-inflammatory mediators) and oxidative stress (increased expression of NADPH oxidase and ROS production) along with the destruction of ZO-1 tight junction protein. Once the damage was clarified, we investigated the therapeutic potential of carnosine, an endogenous dipeptide that is known to be reduced in AMD patients. Our findings demonstrate that carnosine was able to counteract most of the molecular alterations induced by the challenge of ARPE-19 with Aβ oligomers. These new findings obtained with ARPE-19 cells challenged with Aβ1-42 oligomers, along with the well-demonstrated multimodal mechanism of action of carnosine both in vitro and in vivo, able to prevent and/or counteract the dysfunctions elicited by Aβ oligomers, substantiate the neuroprotective potential of this dipeptide in the context of AMD pathology.

Funder

University of Catania

Italian Ministry of Health Research Program

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3