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Induction of Neurotrophic Factors GDNF and BDNF Associated with the Mechanism of Neurorescue Action of Rasagiline and Ladostigil
Author(s) -
WEINREB ORLY,
AMIT TAMAR,
BARAM ORIT,
YOUDIM MOUSSA B.H.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1403.011
Subject(s) - neurotrophic factors , glial cell line derived neurotrophic factor , neuroprotection , neurodegeneration , neuroscience , rasagiline , tropomyosin receptor kinase b , neurotrophin , mechanism of action , pharmacology , parkinson's disease , biology , medicine , disease , receptor , biochemistry , in vitro
Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative disorders, although there is no drug or therapeutic treatment to demonstrate disease‐modifying effects. Previous work has proposed that neurodegeneration is linked to a lack of trophic support in those neurons and brain areas associated with PD and AD. Indeed, previous studies have found that neurotrophic factors (NTFs) support neuronal survival in various cellular and animal models of PD and AD. Thus, attention has begun to turn to the possibility of NTF neuroprotective–neurorescue therapies for these diseases, indicating that NTFs may be of significant clinical importance as exogenously supplied or endogenously induced elements that obliterate neuronal deficits and degeneration. We have recently reported that the anti‐PD drug rasagiline, the anti‐AD drug ladostigil, and their propargyl moiety, propargylamine, enhanced the expression levels of brain‐derived neurotrophic factor and glial cell line–derived neurotrophic factor, endogenous NTFs associated with activation of phosphatidylinositol 3‐kinase, protein kinase, and mitogen‐activated protein kinase cell signaling/survival pathways. These studies indicate that the induction of NTFs by rasagiline and ladostigil might suppress apoptosis and induce neurorescue in neurodegenerative disorders and may support the drugs' possible disease‐modifying mechanism of action.