Tags

Type your tag names separated by a space and hit enter

L-DOPA: a scapegoat for accelerated neurodegeneration in Parkinson's disease?
Prog Neurobiol. 2011 Sep 01; 94(4):389-407.PN

Abstract

There is consensus that amelioration of the motor symptoms of Parkinson's disease is most effective with L-DOPA (levodopa). However, this necessary therapeutic step is biased by an enduring belief that L-DOPA is toxic to the remaining substantia nigra dopaminergic neurons by itself, or by specific metabolites such as dopamine. The concept of L-DOPA toxicity originated from pre-clinical studies conducted mainly in cell culture, demonstrating that L-DOPA or its derivatives damage dopaminergic neurons due to oxidative stress and other mechanisms. However, the in vitro data remain controversial as some studies showed neuroprotective, rather than toxic action of the drug. The relevance of this debate needs to be considered in the context of the studies conducted on animals and in clinical trials that do not provide convincing evidence for L-DOPA toxicity in vivo. This review presents the current views on the pathophysiology of Parkinson's disease, focusing on mitochondrial dysfunction and oxidative/proteolytic stress, the factors that can be affected by L-DOPA or its metabolites. We then critically discuss the evidence supporting the two opposing views on the effects of L-DOPA in vitro, as well as the animal and human data. We also address the problem of inadequate experimental models used in these studies. L-DOPA remains the symptomatic 'hero' of Parkinson's disease. Whether it contributes to degeneration of nigral dopaminergic neurons, or is a 'scapegoat' for explaining undesirable or unexpected effects of the treatment, remains a hotly debated topic.

Authors+Show Affiliations

Department of Physiology and Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd., Auckland 1142, New Zealand. j.lipski@auckland.ac.nzNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

21723913

Citation

Lipski, Janusz, et al. "L-DOPA: a Scapegoat for Accelerated Neurodegeneration in Parkinson's Disease?" Progress in Neurobiology, vol. 94, no. 4, 2011, pp. 389-407.
Lipski J, Nistico R, Berretta N, et al. L-DOPA: a scapegoat for accelerated neurodegeneration in Parkinson's disease? Prog Neurobiol. 2011;94(4):389-407.
Lipski, J., Nistico, R., Berretta, N., Guatteo, E., Bernardi, G., & Mercuri, N. B. (2011). L-DOPA: a scapegoat for accelerated neurodegeneration in Parkinson's disease? Progress in Neurobiology, 94(4), 389-407. https://doi.org/10.1016/j.pneurobio.2011.06.005
Lipski J, et al. L-DOPA: a Scapegoat for Accelerated Neurodegeneration in Parkinson's Disease. Prog Neurobiol. 2011 Sep 1;94(4):389-407. PubMed PMID: 21723913.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-DOPA: a scapegoat for accelerated neurodegeneration in Parkinson's disease? AU - Lipski,Janusz, AU - Nistico,Robert, AU - Berretta,Nicola, AU - Guatteo,Ezia, AU - Bernardi,Giorgio, AU - Mercuri,Nicola B, Y1 - 2011/06/24/ PY - 2011/04/11/received PY - 2011/06/17/revised PY - 2011/06/17/accepted PY - 2011/7/5/entrez PY - 2011/7/5/pubmed PY - 2011/12/13/medline SP - 389 EP - 407 JF - Progress in neurobiology JO - Prog Neurobiol VL - 94 IS - 4 N2 - There is consensus that amelioration of the motor symptoms of Parkinson's disease is most effective with L-DOPA (levodopa). However, this necessary therapeutic step is biased by an enduring belief that L-DOPA is toxic to the remaining substantia nigra dopaminergic neurons by itself, or by specific metabolites such as dopamine. The concept of L-DOPA toxicity originated from pre-clinical studies conducted mainly in cell culture, demonstrating that L-DOPA or its derivatives damage dopaminergic neurons due to oxidative stress and other mechanisms. However, the in vitro data remain controversial as some studies showed neuroprotective, rather than toxic action of the drug. The relevance of this debate needs to be considered in the context of the studies conducted on animals and in clinical trials that do not provide convincing evidence for L-DOPA toxicity in vivo. This review presents the current views on the pathophysiology of Parkinson's disease, focusing on mitochondrial dysfunction and oxidative/proteolytic stress, the factors that can be affected by L-DOPA or its metabolites. We then critically discuss the evidence supporting the two opposing views on the effects of L-DOPA in vitro, as well as the animal and human data. We also address the problem of inadequate experimental models used in these studies. L-DOPA remains the symptomatic 'hero' of Parkinson's disease. Whether it contributes to degeneration of nigral dopaminergic neurons, or is a 'scapegoat' for explaining undesirable or unexpected effects of the treatment, remains a hotly debated topic. SN - 1873-5118 UR - https://www.unboundmedicine.com/medline/citation/21723913/L_DOPA:_a_scapegoat_for_accelerated_neurodegeneration_in_Parkinson's_disease DB - PRIME DP - Unbound Medicine ER -