Identification of potential compounds promoting BDNF production in nigral dopaminergic neurons: clinical implication in Parkinson's disease.
Parkinson's disease (PD) is characterized by the selective loss of dopamine (DA) neurons in the substantia nigral brain region. Currently, there is no cure or treatment that prevents such neuronal loss. Brain-derived neurotrophic factor (BDNF) has been found to support the survival of DA neurons in animal models and in primary cell cultures. However, the large molecular size of BDNF, coupled with the blood brain barrier, prevents its delivery to DA neurons to promote cell survival in the PD brain. The nigral DA neurons have the ability to produce BDNF for neuroprotection via either autocrine or paracrine mechanisms. Low mol. wt compounds were tested to see whether they could increase the production of BDNF in the DA neurons. The compounds tested include neurotransmitters, neuropeptides, intracellular signaling agents, known neuroprotective agents and growth factors. Our results demonstrate that salicyclic acid, cGMP analog, okadaic acid, IBMX, dipyridamole and glutamate significantly enhance BDNF production in DA neuronal cells.
Chun
H S
HS
Department of Neurology and Neuroscience, Weill Medical College of Cornell University at The W.M. Burke Medical Research Institute, White Plains, NY 10605, USA.
Son
J J
JJ
Son
J H
JH
D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy; D015398:Signal Transduction / Q000502:physiology; D013268:Stimulation, Chemical; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D004298:Dopamine