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Titolo:
Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease
Autore:
Du, YS; Ma, ZZ; Lin, SZ; Dodel, RC; Gao, F; Bales, KR; Triarhou, LC; Chernet, E; Perry, KW; Nelson, DLG; Luecke, S; Phebus, LA; Bymaster, FP; Paul, SM;
Indirizzi:
Indiana Univ, Sch Med, Dept Pharmacol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 rmacol, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Dept Toxicol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 oxicol, Indianapolis, IN 46202 USA Univ Marburg, Dept Neurol, D-35033 Marburg, Germany Univ Marburg MarburgGermany D-35033 pt Neurol, D-35033 Marburg, Germany Eli Lilly & Co, Lilly Res Labs, Neurosci Disovery Res, Indianapolis, IN 46285 USA Eli Lilly & Co Indianapolis IN USA 46285 Res, Indianapolis, IN 46285 USA Indiana Univ, Dept Pathol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 Pathol, Indianapolis, IN 46202 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 25, volume: 98, anno: 2001,
pagine: 14669 - 14674
SICI:
0027-8424(200112)98:25<14669:MPNDNI>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; CEREBELLAR GRANULE CELLS; INDUCED APOPTOSIS; IN-VIVO; BRAIN; NEUROTOXICITY; INHIBITION; TOXICITY; TRANSLOCATION; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Paul, SM Indiana Univ, Sch Med, Dept Pharmacol, Indianapolis, IN 46202 USAIndiana Univ Indianapolis IN USA 46202 ndianapolis, IN 46202 USA
Citazione:
Y.S. Du et al., "Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease", P NAS US, 98(25), 2001, pp. 14669-14674

Abstract

Parkinson's disease is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striataldopamine levels, and consequent extrapyramidal motor dysfunction. We now report that minocycline, a semisynthetic tetracycline, recently shown to have neuroprotective effects in animal models of stroke/ischemic injury and Huntington's disease, prevents nigrostriatal dopaminergic neurodegeneration in the 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Minocycline treatment also blocked dopamine depletion in the striatum as well as in the nucleus accumbens after MPTP administration. The neuroprotective effect of minocycline is associated with marked reductions in inducible NO synthase (iNOS) and caspase 1 expression. In vitro studies using primary cultures of mesencephalic and cerebellar granule neurons(CGN) and/or glia demonstrate that minocycline inhibits both 1-methyl-4-phenylpyridinium (MPP+)-mediated iNOS expression and NO-induced neurotoxicity, but MPP+-induced neurotoxicity is inhibited only in the presence of glia. Further, minocycline also inhibits NO-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) in CGN and the p38 MAPK inhibitor, SB203580, blocks NO toxicity of CGN. Our results suggest that minocycline blocksMPTP neurotoxicity in vivo by indirectly inhibiting MPTP/MPP+-induced glial iNOS expression and/or directly inhibiting NO-induced neurotoxicity, mostlikely by inhibiting the phosphorylation of p38 MAPK. Thus, NO appears to play an important role in MPTP neurotoxicity. Neuroprotective tetracyclinesmay be effective in preventing or slowing the progression of Parkinson's and other neurodegenerative diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/09/20 alle ore 07:15:00