کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5739089 | 1615364 | 2017 | 44 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Expanding the repertoire of L-DOPA's actions: A comprehensive review of its functional neurochemistry
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کلمات کلیدی
TphSubstantia nigra pars reticulataMPTPCOMTDOPACDRNSTN5-HIAA5-hydroxytryptophan3-MTGPiEPN6-OHDAMRNHDCVMAT2MAOAglobus pallidus pars internaglobus pallidus pars externaDSP-4MAOBCatechol-O-Methyl-TransferaseN-(2-chloroethyl)-N-ethyl-2-bromobenzylamine6-Hydroxydopamine5-HTDBH5-HTPAADCGPEDATTTX1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine - 1-methyl-4-phenyl-1،2،3،6-tetrahydropyridine3-methoxytyramine - 3-methoxythyramine3,4-dihydroxyphenylacetic acid - 3،4-دی هیدروکسی فنیل اسیدهای اسید5-hydroxyindolacetic acid - 5-hydroxyindolacetic اسیدl-DOPA - L-DOPASNpc - SNPCSNpr - SNPRStriatum - استریاتومDopamine transporter - انتقال دهنده دوپامینnoradrenaline transporter - انتقال دهنده نورآدرنالینOct - اکتبرParkinson’s disease - بیماری پارکینسونtetrodotoxin - تترو دوتوکسین substantia nigra - توده سیاهsubstantia nigra pars compacta - توده سیاه پارس متراکمPositron emission tomography - توموگرافی گسیل پوزیترونtyrosine hydroxylase - تیروزین هیدروکسیلازorganic cation transporter - حمل و نقل کاتیونی آلیNET - خالصDopamine - دوپامینdopamine β-hydroxylase - دوپامین β-هیدروکسیلازdyskinesia - دیسکینزیSERT - سختSerotonin - سروتونینserotonin transporter - سروتونین حمل کنندهbasal ganglia - عقدههای قاعدهایCSF - مایع مغزی نخاعیCerebrospinal fluid - مایع مغزی نخاعیSelective serotonin reuptake inhibitor - مهار کننده بازجذب سروتونین انتخابیSSRI - مهارکنندههای بازجذب سروتونینmonoamine oxidase A - مونوآمین اکسیداز Amonoamine oxidase B - مونوآمین اکسیداز Bvesicular monoamine transporter 2 - مونوآمین حامل 2noradrenaline - نورآدرنالین entopeduncular nucleus - هسته entopeduncularmedian raphe nucleus - هسته رافائل مرکزیdorsal raphe nucleus - هسته رافهSubthalamic nucleus - هسته ی زیرهالامیکhomovanillic acid - هومووانیلیک اسیدtryptophan hydroxylase - هیدروکسیلاز تریپتوفانHistidine Decarboxylase - هیستیدین دکربوکسیلازPET - پتHVA - چهGlobus pallidus - گوی رنگ پریده، گلوبوس پالیدوس
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Though a multi-facetted disorder, Parkinson's disease is prototypically characterized by neurodegeneration of nigrostriatal dopaminergic neurons of the substantia nigra pars compacta, leading to a severe disruption of motor function. Accordingly, L-DOPA, the metabolic precursor of dopamine (DA), is well-established as a treatment for the motor deficits of Parkinson's disease despite long-term complications such as dyskinesia and psychiatric side-effects. Paradoxically, however, despite the traditional assumption that L-DOPA is transformed in residual striatal dopaminergic neurons into DA, the mechanism of action of L-DOPA is neither simple nor entirely clear. Herein, focussing on its influence upon extracellular DA and other neuromodulators in intact animals and experimental models of Parkinson's disease, we highlight effects other than striatal generation of DA in the functional profile of L-DOPA. While not excluding a minor role for glial cells, L-DOPA is principally transformed into DA in neurons yet, interestingly, with a more important role for serotonergic than dopaminergic projections. Moreover, in addition to the striatum, L-DOPA evokes marked increases in extracellular DA in frontal cortex, nucleus accumbens, the subthalamic nucleus and additional extra-striatal regions. In considering its functional profile, it is also important to bear in mind the marked (probably indirect) influence of L-DOPA upon cholinergic, GABAergic and glutamatergic neurons in the basal ganglia and/or cortex, while anomalous serotonergic transmission is incriminated in the emergence of L-DOPA elicited dyskinesia and psychosis. Finally, L-DOPA may exert intrinsic receptor-mediated actions independently of DA neurotransmission and can be processed into bioactive metabolites. In conclusion, L-DOPA exerts a surprisingly complex pattern of neurochemical effects of much greater scope that mere striatal transformation into DA in spared dopaminergic neurons. Their further experimental and clinical clarification should help improve both L-DOPA-based and novel strategies for controlling the motor and other symptoms of Parkinson's disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Progress in Neurobiology - Volume 151, April 2017, Pages 57-100
Journal: Progress in Neurobiology - Volume 151, April 2017, Pages 57-100
نویسندگان
Philippe De Deurwaerdère, Giuseppe Di Giovanni, Mark J. Millan,