 |
 |
Ray -- Am I reading your two posts re neuroimmunophilins correctly? The one below says they don't work, and the other one (the Harvard one) seems to say that they do work. ??? Ann Gibbons -----Original Message----- From: Raymond Strand <[log in to unmask]> To: [log in to unmask] <[log in to unmask]> Date: Sunday, April 15, 2001 11:37 PM Subject: PMID: Failure of GPI compounds to display neurotrophic activity > Clinical trials are still under way for these compounds. > >....................................................... > > Eur J Pharmacol 2001 Mar 16;415(2-3):173-80 > >Failure of GPI compounds to display neurotrophic activity in vitro and in vivo. > >Bocquet A, Lorent G, Fuks B, Grimee R, Talaga P, Daliers J, Klitgaard H. > >Preclinical CNS Research, UCB S.A. Pharma Sector, Chemin du Foriest, B-1420, >Braine-l'Alleud, Belgium > >The aim of this study was to evaluate the neurotrophic and neuroprotective >properties of a series of immunophilin ligands and to assess the potential >involvement of FK506 Binding Protein 12 kDa (FKBP12) rotamase inhibition in this >activity. Both FK506 and rapamycin induced a potent inhibition of the FKBP12 >rotamase activity (pIC(50) values of 7.3 and 7.4, respectively) but only a >modest inhibition was observed with >1-(3,3-dimethyl-2-oxo-pentanoyl)-pyrrolidine-2-carboxylic acid >S-3-pyridin-3-yl-propyl ester (GPI 1046) (5.8), its N-oxide (5.4) and thioester >(6.3) analogues. Compared to nerve growth factor, all these immunophilin ligands >only induced marginal increases in neurite outgrowth of rat dissociated newborn >dorsal root ganglia cells. Furthermore, systemic administration of GPI 1046 and >its N-oxide and thioester analogues failed to prevent striatal dopamine >depletion induced by acute or chronic i.p. treatment with 1-methyl-4-phenyl >1,2,3,6 tetrahydropyridine (MPTP). These results suggest that inhibition of >FKBP12 rotamase activity is not predictive for neurotrophic and neuroprotective >properties of immunophilin ligands and question their therapeutic utility in >neurodegenerative diseases like Parkinson's disease. > >PMID: 11274996 [PubMed - indexed for MEDLINE] > > ....................................................... > > Ray Strand > Prairie Sky Design > -----------------( on the Edge of the Prairie Abyss )--------------- > when the sky is clear > the ground is visible > > 49/dx PD 2 yrs/40? onset/retired > >---------------------------------------------------------------------- >To sign-off Parkinsn send a message to: mailto:[log in to unmask] >In the body of the message put: signoff parkinsn ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn