N-methylation underlying Parkinson's disease
Identifieur interne : 003494 ( Main/Exploration ); précédent : 003493; suivant : 003495N-methylation underlying Parkinson's disease
Auteurs : Kazuo Matsubara [Japon] ; Koji Aoyama [Japon] ; Manabu Suno [Japon] ; Toshio Awaya [Japon]Source :
- Neurotoxicology and teratology [ 0892-0362 ] ; 2002.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
The discovery of 1-methyl-4-phenyl-1,2,2,6-tetrahydropyridine (MPTP) leads to the hypothesis that Parkinson's disease (PD) is may be initiated or precipitated by environmental or endogenous toxins by the mechanism similar to that of MPTP in genetically-predisposed individuals. Endogenous analogs of MPTP, such as β-carbolines (βCs) and tetrahydroisoquinolines, have been proposed as possible causative candidates causing PD and are bioactivated into potential neurotoxins by N-methylation enzyme(s). These N-methylated βCs and tetrahydroisoquinoline have been higher cerebrospinal levels in parkinsonian patients than age-matched controls. Thus, there is a hypotheses to influence the pathogenesis of PD, that is, the excess enzyme activity to activate neurotoxins, such as N-methyltransferase, might be higher in PDs. Indeed, simple βCs, via N-methylation steps, induced bradykinesia with the decreased dopamine contents in the striatum and midbrain in C57/BL mice. In younger (65 years old) PD patients, the excretion amount of N1-methyl-nicotinamaide was significantly higher than that in younger controls. The protein amount of nicotinamide N-methyltransferase (NNMT) was also significantly higher in younger PD patients than that in younger controls. These findings described here would indicate that the excess N-methylation ability for azaheterocyclic amines, such as βCs, before the onset had been implicated in PD pathogenesis. On the other hand, the contribution of aberrant cytochrome P450 or aldehyde oxidase activity acting on the pyridine ring, that could act as detoxification routes of endogenous neurotoxins, would be small in the etiology of PD.
Affiliations:
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i1="02"><s1>Department of Internal Medicine III, Shimane Medical University</s1><s2>Izumo 693-8501</s2><s3>JPN</s3><sZ>2 aut.</sZ></inist:fA14><country>Japon</country><wicri:noRegion>Izumo 693-8501</wicri:noRegion></affiliation></author><author><name sortKey="Suno, Manabu" sort="Suno, Manabu" uniqKey="Suno M" first="Manabu" last="Suno">Manabu Suno</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical College</s1><s2>Asahikawa 078-8510</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Asahikawa</settlement><region type="prefecture">Hokkaidō</region></placeName><orgName type="university">Université de médecine d'Asahikawa</orgName></affiliation></author><author><name sortKey="Awaya, Toshio" sort="Awaya, Toshio" uniqKey="Awaya T" first="Toshio" last="Awaya">Toshio Awaya</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical College</s1><s2>Asahikawa 078-8510</s2><s3>JPN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Japon</country><placeName><settlement type="city">Asahikawa</settlement><region type="prefecture">Hokkaidō</region></placeName><orgName type="university">Université de médecine d'Asahikawa</orgName></affiliation></author></analytic><series><title level="j" type="main">Neurotoxicology and teratology</title><title level="j" type="abbreviated">Neurotoxicol. teratol.</title><idno type="ISSN">0892-0362</idno><imprint><date when="2002">2002</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Neurotoxicology and teratology</title><title level="j" type="abbreviated">Neurotoxicol. teratol.</title><idno type="ISSN">0892-0362</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Carboline derivatives</term><term>Etiology</term><term>Human</term><term>Methylation</term><term>Parkinson disease</term><term>Pathogenesis</term><term>Toxicity</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Carboline dérivé</term><term>Toxicité</term><term>Méthylation</term><term>Parkinson maladie</term><term>Etiologie</term><term>Pathogénie</term><term>Homme</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The discovery of 1-methyl-4-phenyl-1,2,2,6-tetrahydropyridine (MPTP) leads to the hypothesis that Parkinson's disease (PD) is may be initiated or precipitated by environmental or endogenous toxins by the mechanism similar to that of MPTP in genetically-predisposed individuals. Endogenous analogs of MPTP, such as β-carbolines (βCs) and tetrahydroisoquinolines, have been proposed as possible causative candidates causing PD and are bioactivated into potential neurotoxins by N-methylation enzyme(s). These N-methylated βCs and tetrahydroisoquinoline have been higher cerebrospinal levels in parkinsonian patients than age-matched controls. Thus, there is a hypotheses to influence the pathogenesis of PD, that is, the excess enzyme activity to activate neurotoxins, such as N-methyltransferase, might be higher in PDs. Indeed, simple βCs, via N-methylation steps, induced bradykinesia with the decreased dopamine contents in the striatum and midbrain in C57/BL mice. In younger (65 years old) PD patients, the excretion amount of N<sup>1</sup>-methyl-nicotinamaide was significantly higher than that in younger controls. The protein amount of nicotinamide N-methyltransferase (NNMT) was also significantly higher in younger PD patients than that in younger controls. These findings described here would indicate that the excess N-methylation ability for azaheterocyclic amines, such as βCs, before the onset had been implicated in PD pathogenesis. On the other hand, the contribution of aberrant cytochrome P450 or aldehyde oxidase activity acting on the pyridine ring, that could act as detoxification routes of endogenous neurotoxins, would be small in the etiology of PD.</div></front></TEI><affiliations><list><country><li>Japon</li></country><region><li>Hokkaidō</li></region><settlement><li>Asahikawa</li></settlement><orgName><li>Université de médecine d'Asahikawa</li></orgName></list><tree><country name="Japon"><region name="Hokkaidō"><name sortKey="Matsubara, Kazuo" sort="Matsubara, Kazuo" uniqKey="Matsubara K" first="Kazuo" last="Matsubara">Kazuo Matsubara</name></region><name sortKey="Aoyama, Koji" sort="Aoyama, Koji" uniqKey="Aoyama K" first="Koji" last="Aoyama">Koji Aoyama</name><name sortKey="Awaya, Toshio" sort="Awaya, Toshio" uniqKey="Awaya T" first="Toshio" last="Awaya">Toshio Awaya</name><name sortKey="Suno, Manabu" sort="Suno, Manabu" uniqKey="Suno M" first="Manabu" last="Suno">Manabu Suno</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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