Comparison of neuroprotective and neurorestorative capabilities of rasagiline and selegiline against lactacystin-induced nigrostriatal dopaminergic degeneration

Wen Zhu, Wenjie Xie, Tianhong Pan, Joseph Jankovic, Jun Li, Moussa B.H. Youdim, Weidong Le

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Nigrostriatal neurodegeneration in Parkinson's disease (PD) has been postulated to be caused by various pathological conditions, such as mitochondrial defects, oxidative stress, and ubiquitin-proteasome system (UPS) dysfunction. Pharmacological strategies designed to interfere with these pathological pathways may effectively counteract the degeneration. Rasagiline and selegiline are selective and irreversible monoamine oxidase-B inhibitors that possess significant protective properties on dopamine neurons in various pre-clinical models of PD. In the present study, the neuroprotective and neurorestorative effects of rasagiline and selegiline were compared in an animal model of PD produced by inhibition of the UPS. C57BL/6 male mice were microinjected bilaterally with UPS inhibitor lactacystin (1.25 μg/side), into the medial forebrain bundle. Administration of rasagiline (0.2 mg/kg, i.p. once per day) or selegiline (1 mg/kg, i.p. once per day), started 7 days before or after (up to 28 days) after lactacystin microinjection. We found that both rasagiline and selegiline exerted a significant neuroprotective effect against lactacystin-induced neurodegeneration; but only rasagiline managed to restore the nigrostriatal degeneration. Furthermore, rasagiline showed a modest protection against lactacystin-induced inhibition of proteasomal activity. Our study indicates that compared with selegiline, rasagiline is more potent in protecting neurodegeneration induced by UPS impairment and may, therefore, exert disease-modifying effects in PD.

Original languageEnglish (US)
Pages (from-to)1970-1978
Number of pages9
JournalJournal of Neurochemistry
Volume105
Issue number5
DOIs
StatePublished - Jun 2008

Keywords

  • Lactacystin
  • Neuroprotection
  • Neurorestoration
  • Rasagiline
  • Selegiline
  • Ubiquitin-proteasome system

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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