Neuroprotection in Parkinson's disease: love story or mission impossible?

Parkinson's disease was the first neurodegenerative disease in which a deficient neurotransmitter (dopamine) was successfully replaced by a systemically administered drug (levodopa). However, chronic levodopa therapy is associated with the development of motor and psychiatric complications. Furthermore, the progressive course of the disease is not halted and levodopa-resistant symptoms, such as dementia or postural instability, eventually appear. Most of these problems are related to the progressive nature of Parkinson's disease. Therefore, stopping or slowing the progression of Parkinson's disease is one of the main therapeutic objectives. Since the discovery of1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the early 1980s, the possibility of protecting dopaminergic nigral neurons against the action of toxic insults has attracted the attention of the neurological community. Could Parkinson's disease also be the first neurodegenerative condition with a potential neuroprotective treatment? The promise of rational neuroprotective therapy is generating much excitement and some frustration among researchers. In this article, the state of the art of neuroprotection in Parkinson's disease is reviewed.