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Titolo:
Immunophilin ligands can prevent progressive dopaminergic degeneration in animal models of Parkinson's disease
Autore:
Costantini, LC; Cole, D; Isacson, O;
Indirizzi:
Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, Belmont, MA 02178 USA Harvard Univ Belmont MA USA 02178 uroregenerat Lab, Belmont, MA 02178 USA McLean Hosp, Massachusetts Gen Hosp, Dept Neurol & Psychiat, Belmont, MA 02178 USA McLean Hosp Belmont MA USA 02178 Neurol & Psychiat, Belmont, MA 02178 USA Vertex Pharmaceut Inc, Cambridge, MA USA Vertex Pharmaceut Inc Cambridge MA USA Pharmaceut Inc, Cambridge, MA USA
Titolo Testata:
EUROPEAN JOURNAL OF NEUROSCIENCE
fascicolo: 6, volume: 13, anno: 2001,
pagine: 1085 - 1092
SICI:
0953-816X(200103)13:6<1085:ILCPPD>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
PARTIAL LESION MODEL; NEUROTROPHIC FACTOR; GROWTH-FACTOR; IN-VIVO; INTRASTRIATAL INJECTION; RAT MODEL; NIGROSTRIATAL NEURONS; TYROSINE-HYDROXYLASE; SHORT-TERM; FOLLOW-UP;
Keywords:
animal models; FK-binding proteins; mouse; neuroprotection; neurotrophic factors; rat; substantia nigra;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Isacson, O Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, 115 Mill St, Belmont, MA 02178 USA Harvard Univ 115 Mill St Belmont MA USA 02178 ont, MA 02178 USA
Citazione:
L.C. Costantini et al., "Immunophilin ligands can prevent progressive dopaminergic degeneration in animal models of Parkinson's disease", EUR J NEURO, 13(6), 2001, pp. 1085-1092

Abstract

Slowing or halting the progressive dopaminergic (DA) degeneration in Parkinson's disease (PD) would delay the onset and development of motor symptoms, prolong the efficacy of pharmacotherapies and decrease drug-induced side-effects. We tested the potential of two orally administered novel immunophilin ligands to protect against DA degeneration in two animal models of PD. First, in an MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model, we compared an immunophilin ligand (V-10,367) documented to bind the immunophilin FKBP12 with V-13,661, which does not bind FKBP12. Both molecules could prevent the loss of striatal DA innervation in a dose-dependent fashion during 10 days of oral administration. Second, to determine whether an immunophilin ligand can protect against progressive and slow DA degenerationtypical of PD, an intrastriatal 6-hydroxydopamine-infusion rat model was utilized. Oral treatment with the FKBP12-binding immunophilin ligand began on the day of lesion and continued for 21 days. At this time point, post mortem analyses revealed that the treatment had prevented the progressive lossof DA innervation within the striatum and loss of DA neurons within the substantia nigra, related to functional outcome as measured by rotational behaviour. Notably, DA fibres extending into the area of striatal DA denervation were observed only in rats treated with the immunophilin ligand, indicating neuroprotection or sprouting of spared DA fibres. This is the first demonstration that immunophilin ligands can prevent a slow and progressive DA axonal degeneration and neuronal death in vivo. The effects of orally administered structurally related immunophilin ligands in acute and progressive models of DA degeneration are consistent with the idea that these compoundsmay have therapeutic value in PD.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 16:08:44