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Comparison of neuroprotective and neurorescue capabilities of rasagiline and
selegiline, against lactacystin induced nigrostriatal degeneration
Wen Zhu, Tianhong Pan, Wenjie Xie, Pingyi Xu, Joseph Jankovic,
Moussa B.H. Youdim, Weidong Le
Department of Neurology, Baylor College of Medicine, Houston, Texas, USA Department of Pharmacology, Eve Topf Center of Excellence for Neurodegenerative Diseases Research, Haifa, Israel INTRODUCTION
RESULTS
capabilities of rasagiline or selegiline (p<0.01) and about 30% inhibition ofproteasomal evident in ipsilateral SN (Fig.1, 2, 3). A tests since the 7th day after lactacystin animals were sacrificed (Fig. 5, 6) .
Pretreatment with rasagiline or selegiline selegiline against nigrostriatal deficiency and 34.3%, respectively (p < 0.01).
Comparatively, only rasagiline but not activation with equal potency (Fig. 4).
variety of insults in both in vitro and in against lactacystin-induced inhibition of CONCLUSIONS
study, we explored and compared theneuroprotective failure, while rasagiline is more potent.
the proteasome inhibitor, lactacystin.
METHODS
properties require further investigation.
volume) into medial forebrain bundle(MFB).
Fig.3 Proteasome activity in ventral midbrain REFERENCES
1. McNaught KS, Olanow CW. Protein aggregation in the pathogenesis of familial and sporadic Parkinson's disease. Neurobiol Aging. 2006 Apr;27(4):530-45.
2. Zhang X, Xie W, Qu S, Pan T, Wang X, Le W. Neuroprotection by iron chelator against proteasome inhibitor-induced nigral degeneration. Biochem Biophys Res Commun. 2005 Jul 29;333(2):544-9.
3. Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol 2005;62:241–2484. Diederich NJ, Kalteis K, Stamenkovic M, et al. Efficient internal pallidal stimulation in Gilles de la Tourette syndrome: A case report. Mov Disord 2005.
4. Rascol O, Brooks DJ, Melamed E, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet. 2005;365:947–954. 5. Sagi Y, Mandel S, Amit T, Youdim MB. Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism. 6. Olanow CW. Rationale for considering that propargylamines might be neuroprotective in Parkinson's disease. Neurology. 2006 May 23;66(10 Suppl 4):S69-79. generarion and nigrostriatal deficiencyinduced by lactacystin were indicatedby immunostaining of TH-positive cellsand HPLC assay of DA and itsmetabolites.
CD11b-positive cells were introducedto indicate the microglial activationafter microinjection of lactacystin.

Source: http://baylorcollegeofmedicine.org/neurology/pdf/poster_pdrl_NeuroprotectionNeurorescue.pdf

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