In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin
High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is released during tissue damage from immune and non-immune cells — including microglia and neurons. HMGB1 can contribute to progression of numerous chronic inflammatory and autoimmune diseases which is mediated in part by int...
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Format: | Article |
Language: | English |
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Elsevier
2016-07-01
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Series: | Neurobiology of Disease |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996116300407 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matteo Santoro Walter Maetzler Petros Stathakos Heather L. Martin Markus A. Hobert Tim W. Rattay Thomas Gasser John V. Forrester Daniela Berg Kevin J. Tracey Gernot Riedel Peter Teismann |
spellingShingle |
Matteo Santoro Walter Maetzler Petros Stathakos Heather L. Martin Markus A. Hobert Tim W. Rattay Thomas Gasser John V. Forrester Daniela Berg Kevin J. Tracey Gernot Riedel Peter Teismann In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin Neurobiology of Disease Parkinson's disease MPTP High-mobility group box 1 receptor for advanced glycation endproducts |
author_facet |
Matteo Santoro Walter Maetzler Petros Stathakos Heather L. Martin Markus A. Hobert Tim W. Rattay Thomas Gasser John V. Forrester Daniela Berg Kevin J. Tracey Gernot Riedel Peter Teismann |
author_sort |
Matteo Santoro |
title |
In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin |
title_short |
In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin |
title_full |
In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin |
title_fullStr |
In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin |
title_full_unstemmed |
In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin |
title_sort |
in-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and parkinson's disease which can be attenuated by glycyrrhizin |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2016-07-01 |
description |
High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is released during tissue damage from immune and non-immune cells — including microglia and neurons. HMGB1 can contribute to progression of numerous chronic inflammatory and autoimmune diseases which is mediated in part by interaction with the receptor for advanced glycation endproducts (RAGE). There is increasing evidence from in vitro studies that HMGB1 may link the two main pathophysiological components of Parkinson's disease (PD), i.e. progressive dopaminergic degeneration and chronic neuroinflammation which underlie the mechanistic basis of PD progression.Analysis of tissue and biofluid samples from PD patients, showed increased HMGB1 levels in human postmortem substantia nigra specimens as well as in the cerebrospinal fluid and serum of PD patients. In a mouse model of PD induced by sub-acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), systemic administration of neutralizing antibodies to HMGB1 partly inhibited the dopaminergic cell death, and reduced the increase of RAGE and tumour necrosis factor-alpha. The small natural molecule glycyrrhizin, a component from liquorice root which can directly bind to HMGB1, both suppressed MPTP-induced HMGB1 and RAGE upregulation while reducing MPTP-induced dopaminergic cell death in a dose dependent manner.These results provide first in vivo evidence that HMGB1 serves as a powerful bridge between progressive dopaminergic neurodegeneration and chronic neuroinflammation in a model of PD, suggesting that HMGB1 is a suitable target for neuroprotective trials in PD. |
topic |
Parkinson's disease MPTP High-mobility group box 1 receptor for advanced glycation endproducts |
url |
http://www.sciencedirect.com/science/article/pii/S0969996116300407 |
work_keys_str_mv |
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doaj-4abb6cad582648929eac5ff3eeb821c52021-03-22T12:44:08ZengElsevierNeurobiology of Disease1095-953X2016-07-01915968In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizinMatteo Santoro0Walter Maetzler1Petros Stathakos2Heather L. Martin3Markus A. Hobert4Tim W. Rattay5Thomas Gasser6John V. Forrester7Daniela Berg8Kevin J. Tracey9Gernot Riedel10Peter Teismann11School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD Scotland, UKCenter of Neurology, Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany; German Center for Neurodegenerative Diseases (DZNE) Tuebingen, Otfried-Müller-Str. 27, 72076 Tuebingen, GermanySchool of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD Scotland, UKSchool of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD Scotland, UKCenter of Neurology, Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany; German Center for Neurodegenerative Diseases (DZNE) Tuebingen, Otfried-Müller-Str. 27, 72076 Tuebingen, GermanyCenter of Neurology, Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany; German Center for Neurodegenerative Diseases (DZNE) Tuebingen, Otfried-Müller-Str. 27, 72076 Tuebingen, GermanyCenter of Neurology, Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany; German Center for Neurodegenerative Diseases (DZNE) Tuebingen, Otfried-Müller-Str. 27, 72076 Tuebingen, GermanySchool of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD Scotland, UK; Ocular Immunology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Western Australia 6009, Australia; Centre for Experimental Immunology, Lions Eye Institute, Nedlands, Western Australia 6009, AustraliaCenter of Neurology, Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany; German Center for Neurodegenerative Diseases (DZNE) Tuebingen, Otfried-Müller-Str. 27, 72076 Tuebingen, GermanyFeinstein Institute for Medical Research, Manhasset, NY 11030, USASchool of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD Scotland, UKSchool of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD Scotland, UK; Corresponding author at: University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK.High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is released during tissue damage from immune and non-immune cells — including microglia and neurons. HMGB1 can contribute to progression of numerous chronic inflammatory and autoimmune diseases which is mediated in part by interaction with the receptor for advanced glycation endproducts (RAGE). There is increasing evidence from in vitro studies that HMGB1 may link the two main pathophysiological components of Parkinson's disease (PD), i.e. progressive dopaminergic degeneration and chronic neuroinflammation which underlie the mechanistic basis of PD progression.Analysis of tissue and biofluid samples from PD patients, showed increased HMGB1 levels in human postmortem substantia nigra specimens as well as in the cerebrospinal fluid and serum of PD patients. In a mouse model of PD induced by sub-acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), systemic administration of neutralizing antibodies to HMGB1 partly inhibited the dopaminergic cell death, and reduced the increase of RAGE and tumour necrosis factor-alpha. The small natural molecule glycyrrhizin, a component from liquorice root which can directly bind to HMGB1, both suppressed MPTP-induced HMGB1 and RAGE upregulation while reducing MPTP-induced dopaminergic cell death in a dose dependent manner.These results provide first in vivo evidence that HMGB1 serves as a powerful bridge between progressive dopaminergic neurodegeneration and chronic neuroinflammation in a model of PD, suggesting that HMGB1 is a suitable target for neuroprotective trials in PD.http://www.sciencedirect.com/science/article/pii/S0969996116300407Parkinson's diseaseMPTPHigh-mobility group box 1receptor for advanced glycation endproducts |