Revelation in the neuroprotective functions of rasagiline and selegiline: the induction of distinct genes by different mechanisms

Abstract

In Parkinson’s disease, cell death of dopamine neurons in the substantia nigra progresses and neuroprotective therapy is required to halt neuronal loss. In cellular and animal models, selegiline [(-)deprenyl] and rasagiline, inhibitors of type B monoamine oxidase (MAO)-B, protect neuronal cells from programmed cell death. In this paper, the authors review their recent results on the molecular mechanisms by which MAO inhibitors prevent the cell death through the induction of antiapoptotic, prosurvival genes. MAO-A mediates the induction of antiapoptotic bcl-2 and mao-a itself by rasagiline, whereas a different mechanism is associated with selegiline. Rasagiline and selegiline preferentially increase GDNF and BDNF in nonhuman primates and Parkinsonian patients, respectively. Enhanced neurotrophic factors might be applicable to monitor the neurorescuing activity of neuroprotection.

Keywords::

• apoptosis
• Bcl-2
• BDNF
• GDNF
• neuroprotection
• Parkinson’s disease
• programmed cell death
• rasagiline
• selegiline
• type A and B monoamine oxidase

Financial & competing interests disclosure

This work was supported by the Research Grant for Longevity Sciences (21A-13) from the Ministry of Health, Labour and Welfare, Japan (to W Maruyama and M Naoi), and the Promotion of Fundamental Studies in Health Sciences of National Institute of Biomedical Innovation, Japan (to W Maruyama). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.