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Antiapoptotic Properties of Rasagiline, N ‐Propargylamine‐1( R )‐aminoindan, and Its Optical ( S )‐Isomer, TV1022
Author(s) -
MARUYAMA WAKAKO,
YOUDIM MOUSSA B.H.,
NAOI MAKOTO
Publication year - 2001
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 - 10.1111/j.1749-6632.2001.tb03641.x
Subject(s) - rasagiline , neuroprotection , mitochondrial permeability transition pore , apoptosis , chemistry , peroxynitrite , mitochondrion , membrane permeability , membrane potential , oxidative stress , pharmacology , microbiology and biotechnology , biophysics , biochemistry , membrane , biology , parkinson's disease , programmed cell death , medicine , enzyme , disease , superoxide
A bstract : Rasagiline and structurally related propargylamines protected dopaminergic SH‐SY5Y cells from apoptosis induced by 6‐OHDA and peroxynitrite‐generating SIN‐1. It was suggested that the intracellular mechanism of the neuroprotection is related to the stabilization of mitochondrial membrane potential, as indicated by use of a fluorescent indicator, JC‐1. The opening of the permeability transition pore (PTP) was prevented by rasagiline, even in isolated mitochondria. The activation of apoptotic cascade by the oxidative stress and neurotoxins, such as activation of caspase 3 and DNA fragmentation, was also inhibited by pretreatment with rasagiline. These propargylamines may prevent or rescue declining neurons induced by mitochondrial apoptotic cascade and may be applicable as “neuroprotective agents” in aging and age‐related neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases.