Neuroprotection has been proposed in
neurodegenerative disorders, such as Parkinson's and
Alzheimer's diseases, to delay or halt
disease progression or reverse neuronal deterioration. The inhibitors of
type B monoamine oxidase (
MAO),
rasagiline and (-)
deprenyl, prevent neuronal loss in cellular and animal models of
neurodegenerative disorders by intervening in the death signal pathway in mitochondria. In addition,
rasagiline and (-)
deprenyl increase the expression of anti-apoptotic Bcl-2
protein family and
neurotrophic factors.
Neurotrophic factors, especially
glial cell line-derived neurotrophic factor (
GDNF) and brain-derived derived
neurotrophic factor (
BDNF), are required not only for growth and maintenance of developing neurons, but also for function and plasticity of distinct population of adult neurons.
GDNF and
BDNF have been reported to reduce Parkinson and
Alzheimer's diseases, respectively.
GDNF protects the nigra-striatal dopamine neurons in animal models of
Parkinson's disease, and its administration has been tried as a disease-modifying
therapy for parkinsonian patients. However, the results of clinical trials have not been fully conclusive and more practical ways to enhance
GDNF levels in the targeted neurons are essentially required for future clinical application.
Rasagiline and (-)
deprenyl induced preferentially
GDNF and
BDNF in cellular and non-human primate experiments, and (-)
deprenyl increased
BDNF level in the cerebrospinal fluid of parkinsonian patients. In this paper, we review the induction of
GDNF and
BDNF by these
MAO inhibitors as a strategy of neuroprotective
therapy. The induction of prosurvival genes is discussed in relation to a possible disease-modifying
therapy with
MAO inhibitors in
neurodegenerative disorders.