Abstract
Neuroprotection refers to the protection of neurons from excitotoxicity, oxidative stress and apoptosis as principal mechanisms of cell loss in a variety of diseases of the central nervous system. Our interest in Parkinson’s disease (PD) treatment is focused on drugs with neuroprotective properties in preclinical experiments and evidence-based efficacy in human subjects. To this date, neuroprotection has never been solidly proven in clinical trials but recent adequate markers and/or strategies to study and promote this important goal are described. A myriad of compounds with protective properties in cell cultures and animal models yield to few treatments in clinical practice. At present, markers of neuronal vitality, disease modifying effects and long term clinical stability are the elements searched for in clinical trials. This review highlights new strategies to monitor patients with PD. Currently, neuroprotection in subjects has not been solidly achieved for selegiline and pramipexole; however, a recent rasagiline trial design is showing new indications of disease course modifying effects. In neurological practice, it is of utmost importance to take into account the potential neuroprotection exerted by a treatment in conjunction with its symptomatic efficacy.
Highlights
Multiple neuronal systems are involved, the hallmark of Parkinson’s disease (PD) pathology is centered on cell loss in substantia nigra pars compacta (SNc) directly affecting the dopaminergic nigro-striatal pathway
Among the drugs that have received most of the attention in relation to neuroprotection, selegiline and rasagiline stand out, which are monoamine oxidase type-B (MAO-B) inhibitors
Drugs that have already been approved in PD for their symptomatic effects, such as dopamine agonists or propargylamines, offer the best opportunity for establishing the neuroprotective feature of a drug, even if the observed benefits lie within their symptomatic properties
Summary
Multiple neuronal systems are involved, the hallmark of Parkinson’s disease (PD) pathology is centered on cell loss in substantia nigra pars compacta (SNc) directly affecting the dopaminergic nigro-striatal pathway. Strategies to monitor dopamine nerve terminals in vivo in PD brains include striatal uptake of (18)fluorodopa or (11)C-beta-CFT [2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane] revealed, by positron emission tomography (PET) [1, 2, 3] and beta-CIT or (123)I in single-photon emission computerized tomography (SPECT), to show distribution of dopamine transporters (DAT), among other tracer-DAT ligands [4, 5]. It has not yet been confirmed that striatal uptake of these isotopes does correlate with the remaining number of dopamine neurons or terminals. Based on the possible interventions available for protecting vulnerable neurons, different strategies and treatment algorithms have been presented [9, 10]. In 2003, twelve potentially neuroprotective compounds were prioritized by a large expert group, the CINAPS
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