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
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
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
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.
Law Council Diversity Policy DIVERSITY POLICY This policy provides the framework by which the Law Council actively manages and encourages diversity and inclusion across the organisation. This is an organisational policy only, and does not of itself give rise to any cause of action. This policy should be read in conjunction with the Law Council’s: Company Policies, including concerni