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      Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?

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          Abstract

          Neurodegenerative disorders show an increasing prevalence in a number of highly developed countries. Often, these diseases require life-long treatment mostly with drugs which are costly and mostly accompanied by more or less serious side-effects. Their heterogeneous manifestation, severity and outcome pose the need for individualised treatment options. There is an intensive search for new strategies not only for treating but also for preventing these diseases. Green tea and green tea extracts seem to be such a promising and safe alternative. However, data regarding the beneficial effects and possible underlying mechanism, specifically in clinical trials, are rare and rather controversial or non-conclusive. This review outlines the existing evidence from preclinical studies (cell and tissue cultures and animal models) and clinical trials regarding preventive and therapeutic effects of epigallcatechin-3-gallate in neurodegenerative diseases and considers antioxidative vs. pro-oxidative properties of the tea catechin important for dosage recommendations.

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          Most cited references199

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          Cortical demyelination and diffuse white matter injury in multiple sclerosis.

          Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. New and active focal inflammatory demyelinating lesions in the white matter were mainly present in patients with acute and relapsing multiple sclerosis, while diffuse injury of the NAWM and cortical demyelination were characteristic hallmarks of primary and secondary progressive multiple sclerosis. Cortical demyelination and injury of the NAWM, reflected by diffuse axonal injury with profound microglia activation, occurred on the background of a global inflammatory response in the whole brain and meninges. There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination.
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            EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity.

            Protein misfolding and formation of beta-sheet-rich amyloid fibrils or aggregates is related to cellular toxicity and decay in various human disorders including Alzheimer's and Parkinson's disease. Recently, we demonstrated that the polyphenol (-)-epi-gallocatechine gallate (EGCG) inhibits alpha-synuclein and amyloid-beta fibrillogenesis. It associates with natively unfolded polypeptides and promotes the self-assembly of unstructured oligomers of a new type. Whether EGCG disassembles preformed amyloid fibrils, however, remained unclear. Here, we show that EGCG has the ability to convert large, mature alpha-synuclein and amyloid-beta fibrils into smaller, amorphous protein aggregates that are nontoxic to mammalian cells. Mechanistic studies revealed that the compound directly binds to beta-sheet-rich aggregates and mediates the conformational change without their disassembly into monomers or small diffusible oligomers. These findings suggest that EGCG is a potent remodeling agent of mature amyloid fibrils.
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              Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

              Background The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. Methods Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). Results Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. Conclusion This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.
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                Author and article information

                Contributors
                Journal
                EPMA J
                EPMA J
                The EPMA Journal
                BioMed Central
                1878-5077
                1878-5085
                2013
                18 February 2013
                : 4
                : 1
                : 5
                Affiliations
                [1 ]Experimental and Clinical Research Center, a joint cooperation between the Charité University Medicine Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, D-13125, Germany
                [2 ]NeuroCure Clinical Research Center, Charité University Medicine, Berlin, D-10117, Germany
                [3 ]Department of Molecular Pharmacology, Faculty of Medicine, Eve Topf Center of Excellence for Neurodegenerative Diseases Research and Department of Molecular Pharmacology, Faculty of Medicine, Technion, Haifa, 31905, Israel
                [4 ]Medizinische Klinik für Kardiologie und Angiologie, Charité University Medicine Berlin, Campus Mitte, Berlin, D-10117, Germany
                [5 ]Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, Geneva, CH-1211, Switzerland
                [6 ]Department of Proteomics and Molecular Mechanisms of Neurodegenerative Diseases, Max Delbrueck Center for Molecular Medicine, Berlin, D-13125, Germany
                Article
                1878-5085-4-5
                10.1186/1878-5085-4-5
                3585739
                23418936
                9f7ca05d-a268-4cf0-928b-5e0a11ec86ff
                Copyright ©2013 Mähler et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 December 2012
                : 25 January 2013
                Categories
                Review

                Molecular medicine
                neurological diseases,predictive and personalised medicine,targeted prevention,green tea,epigallocatechin-3-gallate,tailored therapy

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