Neuroprotection for Parkinson's disease: a new approach for a new millennium

B Drukarch, F L van Muiswinkel

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Parkinson's disease (PD) is the only neurodegenerative disorder in which pharmacological intervention has resulted in a marked decrease in morbidity and a significant delay in mortality. However, the medium to long-term efficacy of this pharmacotherapy, mainly consisting of dopaminomimetics like L -dopa and dopamine receptor agonists, suffers greatly from the unrelenting progression of the disease process underlying PD, i.e., the degeneration of neuromelanin-containing, dopaminergic neurones in the substantia nigra. Efforts concentrated on understanding the mechanisms of dopaminergic cell death in Parkinson's disease have led to identification of a large variety of pathogenetic factors, including excessive release of oxygen free radicals during enzymatic dopamine breakdown, impairment of mitochondrial function, production of inflammatory mediators, loss of trophic support, and apoptosis. Therapeutic approaches aimed at correcting these abnormalities are currently being evaluated on their efficacy as neuroprotectants for PD. Here, we focus on the process of dopamine auto-oxidation, the chain of reactions leading to the formation of neuromelanin, as an often overlooked, yet obvious pathogenetic factor. In particular, we discuss the option of drug-mediated stimulation of endogenous mechanisms responsible for the detoxification of dopamine auto-oxidation products as a novel means of neuroprotection in Parkinson's disease.

Original languageEnglish
Pages (from-to)1855-68
Number of pages14
JournalExpert Opinion on Investigational Drugs
Volume10
Issue number10
DOIs
Publication statusPublished - Oct 2001

Cite this

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title = "Neuroprotection for Parkinson's disease: a new approach for a new millennium",
abstract = "Parkinson's disease (PD) is the only neurodegenerative disorder in which pharmacological intervention has resulted in a marked decrease in morbidity and a significant delay in mortality. However, the medium to long-term efficacy of this pharmacotherapy, mainly consisting of dopaminomimetics like L -dopa and dopamine receptor agonists, suffers greatly from the unrelenting progression of the disease process underlying PD, i.e., the degeneration of neuromelanin-containing, dopaminergic neurones in the substantia nigra. Efforts concentrated on understanding the mechanisms of dopaminergic cell death in Parkinson's disease have led to identification of a large variety of pathogenetic factors, including excessive release of oxygen free radicals during enzymatic dopamine breakdown, impairment of mitochondrial function, production of inflammatory mediators, loss of trophic support, and apoptosis. Therapeutic approaches aimed at correcting these abnormalities are currently being evaluated on their efficacy as neuroprotectants for PD. Here, we focus on the process of dopamine auto-oxidation, the chain of reactions leading to the formation of neuromelanin, as an often overlooked, yet obvious pathogenetic factor. In particular, we discuss the option of drug-mediated stimulation of endogenous mechanisms responsible for the detoxification of dopamine auto-oxidation products as a novel means of neuroprotection in Parkinson's disease.",
keywords = "Animals, Disease Progression, Humans, Neuroprotective Agents, Oxidative Stress, Parkinson Disease, Journal Article, Review",
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pages = "1855--68",
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Neuroprotection for Parkinson's disease : a new approach for a new millennium. / Drukarch, B; van Muiswinkel, F L.

In: Expert Opinion on Investigational Drugs, Vol. 10, No. 10, 10.2001, p. 1855-68.

Research output: Contribution to journalReview articleAcademicpeer-review

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AB - Parkinson's disease (PD) is the only neurodegenerative disorder in which pharmacological intervention has resulted in a marked decrease in morbidity and a significant delay in mortality. However, the medium to long-term efficacy of this pharmacotherapy, mainly consisting of dopaminomimetics like L -dopa and dopamine receptor agonists, suffers greatly from the unrelenting progression of the disease process underlying PD, i.e., the degeneration of neuromelanin-containing, dopaminergic neurones in the substantia nigra. Efforts concentrated on understanding the mechanisms of dopaminergic cell death in Parkinson's disease have led to identification of a large variety of pathogenetic factors, including excessive release of oxygen free radicals during enzymatic dopamine breakdown, impairment of mitochondrial function, production of inflammatory mediators, loss of trophic support, and apoptosis. Therapeutic approaches aimed at correcting these abnormalities are currently being evaluated on their efficacy as neuroprotectants for PD. Here, we focus on the process of dopamine auto-oxidation, the chain of reactions leading to the formation of neuromelanin, as an often overlooked, yet obvious pathogenetic factor. In particular, we discuss the option of drug-mediated stimulation of endogenous mechanisms responsible for the detoxification of dopamine auto-oxidation products as a novel means of neuroprotection in Parkinson's disease.

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