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

Autor: 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
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
TNF-α
tumour necrosis factor-alpha
Parkinson's disease
metabolism [Tumor Necrosis Factor-alpha]
TH
tyrosine-hydroxylase
drug effects [Dopaminergic Neurons]
metabolism [Microglia]
drug effects [Microglia]
PD
Parkinson's disease
pharmacology [1-Methyl-4-phenyl-1
2
3
6-tetrahydropyridine]
HMGB1 Protein
Aged
80 and over
Cell Death
metabolism [Dopaminergic Neurons]
Parkinson Disease
Middle Aged
SNpc
substantia nigra pars compacta
Neuroprotective Agents
Neurology
1-Methyl-4-phenyl-1
2
3
6-tetrahydropyridine
HMGB1 protein
mouse
Female
Microglia
Wt
wild type
HMGB1
high-mobility group box 1
metabolism [Parkinson Disease]
MPTP
1-methyl-4-phenyl-1
2
3
6-tetrahydropyridine
chemical and pharmacologic phenomena
pharmacology [Glycyrrhizic Acid]
Article
lcsh:RC321-571
RAGE
receptor for advanced glycation endproducts
High-mobility group box 1
receptor for advanced glycation endproducts
ddc:570
HVA
homovanillic acid
Animals
Humans
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
MPTP
Aged
CSF
Cerebrospinal fluid
HMGB1 protein
human
pharmacology [Neuroprotective Agents]
Tumor Necrosis Factor-alpha
Dopaminergic Neurons
GFAP
glial fibrillary acidic protein
metabolism [HMGB1 Protein]
drug effects [Cell Death]
Glycyrrhizic Acid
drug therapy [Parkinson Disease]
DOPAC
3
4-Dihydroxyphenylacetic acid
COX
cyclooxygenase
MPP+
1-methyl-4-phenylpyridinium
Mice
Inbred C57BL
OD
optical density
Disease Models
Animal
H&Y
Hoehn & Yahr
Zdroj: Neurobiology of Disease
Neurobiology of disease 91, 59-68 (2016). doi:10.1016/j.nbd.2016.02.018
Neurobiology of Disease, Vol 91, Iss, Pp 59-68 (2016)
ISSN: 1095-953X
0969-9961
DOI: 10.1016/j.nbd.2016.02.018
Popis: 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.
Highlights • HMGB1 is up-regulated in Parkinson's disease. • HMGB1 is translocalized into the cytoplasm after MPTP. • Inhibition of HMGB1 protects against MPTP-toxicity. • Translocalization of HMGB1 is reduced after inhibition a neutralizing antibody or glycyrrhizin.
Databáze: OpenAIRE
Externí odkaz: