| Summary: | The relationship between two pathological hallmarks of Parkinson’s disease (PD), i.e. selective loss of dopaminergic cells in the substantia nigra pars compacta (SNc) and intracytoplasmic aggregation of α-synuclein (αS) protein in Lewy bodies (LBs) in the surviving nerve cells, is still unresolved. Although levodopa (l-dopa), the natural amino acid precursor of dopamine, is the most effective and widely used symptomatic agent for the treatment of PD, there has been a long-standing concern that it could be toxic to dopaminergic neurons. This is because some in vitro studies have reported that l-dopa enhances oxidative stress and/or can modulate the aggregation process of αS. Despite the relevance of these findings to routine clinical practice being highly questionable, they have generated concern and resulted in significant delays in initiating treatment in some instances. This strategy has stemmed from fear of motor complications such as dyskinesia and wearing-off responses as well as concern that exogenous l-dopa may be neurotoxic. Here, we elaborate on our unique clinico-pathological study examining the effect of antecedent drug exposure to the changes seen post mortem that provided further evidence that concerns over l-dopa neurotoxicity in PD patients are not warranted.
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