Antiapoptotic properties of rasagiline, N-propargylamine-1(R)-aminoindan, and its optical (S)-isomer, TV1022.
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.
Maruyama
W
W
Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Aichi, Japan.
Youdim
M B
MB
Naoi
M
M
D018663:Adrenergic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D006801:Humans; D007189:Indans / Q000737:chemistry / Q000494:pharmacology*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D010293:Pargyline / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D011437:Propylamines / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D018663:Adrenergic Agents; D007189:Indans; D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D011437:Propylamines; C031967:rasagiline; C009054:propargylamine; C002385:linsidomine; D016627:Oxidopamine; D010293:Pargyline; D008981:Molsidomine