Rationale for considering that propargylamines might be neuroprotective in Parkinson's disease
by
Olanow CW.
Department of Neurology,
Mount Sinai School of Medicine,
New York, NY 10029, USA.
warren.olanow@mssm.edu
Neurology. 2006 May 23;66(10 Suppl 4):S69-79.


ABSTRACT

P Rationale for considering that propargylamines might be neuroprotective in Parkinson's disease. A neuroprotective therapy that slows or stops disease progression is the major unmet medical need in Parkinson's disease (PD). Current evidence indicates that cell death in PD occurs, at least in part, by way of a signal-mediated apoptotic process. This raises the possibility that anti-apoptotic agents might be neuroprotective in PD. Propargylamines have been demonstrated to be potent anti-apoptotic agents in both in vitro and in vivo studies, presumably by maintaining glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a dimer and thereby preventing its nuclear translocation where it blocks upregulation of anti-apoptotic proteins. Selegiline is a monamine oxidase type B (MAO-B) inhibitor that incorporates a propargyl ring within its molecular structure. It was shown to delay the need for symptomatic therapy in untreated PD patients in the DATATOP study, but interpretation is confounded by its symptomatic effects. Rasagiline is another MAO-B inhibitor that contains a propargyl ring and has protective effects in laboratory models. A clinical trial utilizing a delayed start design demonstrated that patients initiated on rasagiline at baseline are improved at one year in comparison to patients initiated on placebo and switched to rasagiline at 6 months even though both groups were on the same treatment for the last 6 months of the study. These results argue against the benefit being due to a symptomatic effect and are consistent with rasagiline having a protective effect.


MAOIs
Rasagiline
Neuroprotection
Rasagiline: structure
MAO-b inhibitors/PD
Anti-apoptotic activity
Molecular mechanisms
Rasagiline pharmacology
Induction of pro-survival genes
Rasagiline and the mitochondria
Antioxidant strategies against aging
Anti-Alzheimer/anti-Parkinson's drugs
Rasagiline versus selegiline metabolites
Rasagiline/ anti-apoptotic bcl-2 gene family
Dual AChE and MAO inhibitors and Alzheimer's
Rasagiline v selegiline: neuronal survival effects
Rasagiline (Agilect) in early Parkinson's disease


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