An anti-Parkinson's disease drug, N-propargyl-1(R)-aminoindan (rasagiline), enhances expression of anti-apoptotic Bcl-2 in human dopaminergic SH-SY5Y cells

@article{Akao2002AnAD,
  title={An anti-Parkinson's disease drug, N-propargyl-1(R)-aminoindan (rasagiline), enhances expression of anti-apoptotic Bcl-2 in human dopaminergic SH-SY5Y cells},
  author={Yukihiro Akao and Wakako Maruyama and Hong Yi and Masayo Shamoto-Nagai and Moussa B. H. Youdim and Makoto Naoi},
  journal={Neuroscience Letters},
  year={2002},
  volume={326},
  pages={105-108}
}
N-Propargyl-1(R)-aminoindan (rasagiline) is now under phase III clinical trials for Parkinson's disease (PD), and it rescues dopamine neurons from cell death in animal and cellular models of PD. Recently, we proved that rasagiline protected dopaminergic SH-SY5Y cells against apoptosis induced by a dopaminergic neurotoxin, N-methyl(R)salsolinol, and the mechanism was clarified to be due to suppression of death signal transduction in mitochondria. In this paper, the effects of rasagiline on the… 
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N-Propargyl-l(R)-aminoindan, rasagiline, an anti-Parkinson drug, was found to increase the protein and mRNA levels of glial cell line-derived neurotrophic factor (GDNF) in human neuroblastoma SH-SY5Y
N-Propargylamine protects SH-SY5Y cells from apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, through stabilization of mitochondrial membrane and induction of anti-apoptotic Bcl-2
TLDR
The neuroprotective activity of free N-propargylamine was studied using SH-SY5Y cells expressing only type A monoamine oxidase (MAO) against apoptosis induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, indicating that MAO inhibition is not prerequisite for the protective function of N-PropargYlamine.
Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its derivatives
TLDR
Structural activity studies have shown that the neuroprotective activity is associated with the propargyl moiety of rasagiline which protects mitochondrial viability and MPTp by activating Bcl-2 and protein kinase C (PKC), and down regulating pro-apoptotic FAS and Bax.
Neuroprotection by propargylamines in Parkinson's disease: intracellular mechanism underlying the anti-apoptotic function and search for clinical markers.
TLDR
DNA array studies indicate that rasagiline increases the expression of the genes coding mitochondrial energy synthesis, inhibitors of apoptosis, transcription factors, kinases and ubiquitin-proteasome system, sequentially in a time-dependent way.
Rasagiline: A novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity
TLDR
It is demonstrated that the major metabolite of rasagiline, 1-(R)-aminoindan has antioxidant and neuroprotective capabilities and thus, may contribute to the overt activity of its parent compound, rasgiline.
Rasagiline: an anti-Parkinson drug with neuroprotective activity
  • M. Youdim
  • Chemistry, Medicine
    Expert review of neurotherapeutics
  • 2003
TLDR
Rasagiline is a novel neuroprotective–antiapoptotic second-generation potent irreversible selective inhibitor of monoamine oxidase B that prevents the neurotoxin-initiated demise of mitochondria via modulation of cell survival/death Bcl-2 family proteins at the mitochondria permeability transition pore.
Rasagiline in treatment of Parkinson’s disease
TLDR
Analysis of delayed-start clinical trial suggests the potential for disease modification, and further trials are examining this effect of rasagiline as an adjunct to levodopa.
Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson’s disease
TLDR
Recent advances in understanding of the neuroprotection offered by MAOB-Is are presented and possible evaluation of neuroprotective efficacy in clinical samples is discussed.
The importance of propargylamine moiety in the anti‐ Parkinson drug rasagiline and its derivatives for MAPK‐ dependent amyloid precursor protein processing
TLDR
It is demonstrated that MAO‐B inhibition is not a prerequisite for either sAPPα‐induced release or ERK phosphorylation, and structure‐activity relationship among rasagiline‐related compounds suggests the crucial role of the propargyl moiety in these molecules.
Rationale for considering that propargylamines might be neuroprotective in Parkinson’s disease
TLDR
Results argue against the benefit being due to a symptomatic effect and are consistent with rasagiline having a protective effect.
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