Mortalin inhibition in experimental Parkinson's disease

Davide Chiasserini, Alessandro Tozzi, Antonio de Iure, Michela Tantucci, Federica Susta, Pier Luigi Orvietani, Keizo Koya, Luciano Binaglia, Paolo Calabresi

Research output: Contribution to journalArticlepeer-review


Among heat shock proteins, mortalin has been linked to the pathogenesis of Parkinson's disease. In the present work a rat model of Parkinson's disease was used to analyze the expression of striatal proteins and, more specifically, mortalin expression. The possible involvement of mortalin in Parkinson's disease pathogenesis was further investigated by utilizing an electrophysiological approach and pharmacological inhibition of mortalin in both the physiological and the parkinsonian states. Proteomic analysis was used to investigate changes in striatal protein expression in the 6-hydroxydopamine rat model of Parkinson's disease. The electrophysiological effects of MKT-077, a rhodamine-123 analogue acting as an inhibitor of mortalin, were measured by field potential recordings from corticostriatal brain slices obtained from control, sham-operated, and 6-hydroxydopamine-denervated animals. Slices in the presence of rotenone, an inhibitor of mitochondrial complex I, were also analyzed. Proteomic analysis revealed downregulation of mortalin in the striata of 6-hydroxydopamine-treated rats in comparison with sham-operated animals. MKT-077 reduced corticostriatal field potential amplitude in physiological conditions, inducing membrane depolarization and inward current in striatal medium spiny neurons. In addition, we observed that concentrations of MKT-077 not inducing any electrophysiological effect in physiological conditions caused significant changes in striatal slices from parkinsonian animals as well as in slices treated with a submaximal concentration of rotenone. These findings suggest a critical link between mortalin function and mitochondrial activity in both physiological and pathological conditions mimicking Parkinson's disease.

Original languageEnglish
Pages (from-to)1639-1647
Number of pages9
JournalMovement Disorders
Issue number9
Publication statusPublished - Aug 1 2011


  • 6-hydroxydopamine
  • Heat shock protein
  • Mitochondria
  • Mortalin
  • Parkinson's disease
  • Rotenone

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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