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      Neuroprotective Effect of Bergamot Juice in 6-OHDA-Induced SH-SY5Y Cell Death, an In Vitro Model of Parkinson’s Disease

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          Abstract

          Much evidence suggests that both oxidative stress and apoptosis play a key role in the pathogenesis of Parkinson’s disease (PD). The present study aims to evaluate the protective effect of bergamot juice (BJ) against 6-hydroxydopamine (6-OHDA)- or H 2O 2-induced cell death. Treatment of differentiated SH-SY5Y human neuroblastoma cells with 6-OHDA or H 2O 2 resulted in cell death that was significantly reduced by the pre-treatment with BJ. The protective effects of BJ seem to correlate with the reduction of intracellular reactive oxygen species and nitric oxide generation caused by 6-OHDA or H 2O 2. BJ also attenuated mitochondrial dysfunction, caspase-3 activation, imbalance of pro- and anti-apoptotic proteins, MAPKs activation and reduced NF-ĸB nuclear translocation evoked by neurotoxic agents. Additionally, BJ exhibited excellent antioxidant capability in cell-free assays. Collectively, our results suggest that BJ exerts neuroprotective effect through the interplay with specific cell targets and its antioxidant activity, making it worthy of consideration for the management of neurodegenerative diseases.

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          The SH-SY5Y cell line in Parkinson’s disease research: a systematic review

          Parkinson’s disease (PD) is a devastating and highly prevalent neurodegenerative disease for which only symptomatic treatment is available. In order to develop a truly effective disease-modifying therapy, improvement of our current understanding of the molecular and cellular mechanisms underlying PD pathogenesis and progression is crucial. For this purpose, standardization of research protocols and disease models is necessary. As human dopaminergic neurons, the cells mainly affected in PD, are difficult to obtain and maintain as primary cells, current PD research is mostly performed with permanently established neuronal cell models, in particular the neuroblastoma SH-SY5Y lineage. This cell line is frequently chosen because of its human origin, catecholaminergic (though not strictly dopaminergic) neuronal properties, and ease of maintenance. However, there is no consensus on many fundamental aspects that are associated with its use, such as the effects of culture media composition and of variations in differentiation protocols. Here we present the outcome of a systematic review of scientific articles that have used SH-SY5Y cells to explore PD. We describe the cell source, culture conditions, differentiation protocols, methods/approaches used to mimic PD and the preclinical validation of the SH-SY5Y findings by employing alternative cellular and animal models. Thus, this overview may help to standardize the use of the SH-SY5Y cell line in PD research and serve as a future user’s guide. Electronic supplementary material The online version of this article (doi:10.1186/s13024-017-0149-0) contains supplementary material, which is available to authorized users.
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            Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease

            Abstract Parkinson's disease prevalence is rapidly increasing in an aging global population. With this increase comes exponentially rising social and economic costs, emphasizing the immediate need for effective disease‐modifying treatments. Motor dysfunction results from the loss of dopaminergic neurons in the substantia nigra pars compacta and depletion of dopamine in the nigrostriatal pathway. While a specific biochemical mechanism remains elusive, oxidative stress plays an undeniable role in a complex and progressive neurodegenerative cascade. This review will explore the molecular factors that contribute to the high steady‐state of oxidative stress in the healthy substantia nigra during aging, and how this chemical environment renders neurons susceptible to oxidative damage in Parkinson's disease. Contributing factors to oxidative stress during aging and as a pathogenic mechanism for Parkinson's disease will be discussed within the context of how and why therapeutic approaches targeting cellular redox activity in this disorder have, to date, yielded little therapeutic benefit. We present a contemporary perspective on the central biochemical contribution of redox imbalance to Parkinson's disease etiology and argue that improving our ability to accurately measure oxidative stress, dopaminergic neurotransmission and cell death pathways in vivo is crucial for both the development of new therapies and the identification of novel disease biomarkers.
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              The Role of PI3K/Akt and ERK in Neurodegenerative Disorders

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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                05 April 2020
                April 2020
                : 12
                : 4
                : 326
                Affiliations
                [1 ]Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98100 Messina, Italy; nferlazzo@ 123456unime.it (N.F.); scirmi@ 123456unime.it (S.C.); amaugeri@ 123456unime.it (A.M.); cate.russo.22@ 123456gmail.com (C.R.); gelombardo@ 123456unime.it (G.E.L.)
                [2 ]Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy; mollace@ 123456unicz.it
                [3 ]Fondazione “Prof. Antonio Imbesi”, 98100 Messina, Italy
                [4 ]Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy; gangemis@ 123456unime.it
                [5 ]Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98100 Messina, Italy; gcalapai@ 123456unime.it
                Author notes
                [* ]Correspondence: mnavarra@ 123456unime.it
                Author information
                https://orcid.org/0000-0002-6916-0307
                https://orcid.org/0000-0002-6492-7820
                Article
                pharmaceutics-12-00326
                10.3390/pharmaceutics12040326
                7238189
                32260543
                c4322e03-c77a-494c-a9f6-7a8ba0aa05e6
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 March 2020
                : 03 April 2020
                Categories
                Article

                citrus bergamia,parkinson’s disease,sh-sy5y cells,natural products,6-ohda,bergamot

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