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Loss of Non-Apoptotic Role of Caspase-3 in the PINK1 Mouse Model of Parkinson's Disease.
Imbriani, Paola; Tassone, Annalisa; Meringolo, Maria; Ponterio, Giulia; Madeo, Graziella; Pisani, Antonio; Bonsi, Paola; Martella, Giuseppina.
Afiliación
  • Imbriani P; Laboratory of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, 00143 Rome, Italy.
  • Tassone A; Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
  • Meringolo M; Laboratory of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, 00143 Rome, Italy.
  • Ponterio G; Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
  • Madeo G; Laboratory of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, 00143 Rome, Italy.
  • Pisani A; Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
  • Bonsi P; Laboratory of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, 00143 Rome, Italy.
  • Martella G; Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Int J Mol Sci ; 20(14)2019 Jul 11.
Article en En | MEDLINE | ID: mdl-31336695
Caspases are a family of conserved cysteine proteases that play key roles in multiple cellular processes, including programmed cell death and inflammation. Recent evidence shows that caspases are also involved in crucial non-apoptotic functions, such as dendrite development, axon pruning, and synaptic plasticity mechanisms underlying learning and memory processes. The activated form of caspase-3, which is known to trigger widespread damage and degeneration, can also modulate synaptic function in the adult brain. Thus, in the present study, we tested the hypothesis that caspase-3 modulates synaptic plasticity at corticostriatal synapses in the phosphatase and tensin homolog (PTEN) induced kinase 1 (PINK1) mouse model of Parkinson's disease (PD). Loss of PINK1 has been previously associated with an impairment of corticostriatal long-term depression (LTD), rescued by amphetamine-induced dopamine release. Here, we show that caspase-3 activity, measured after LTD induction, is significantly decreased in the PINK1 knockout model compared with wild-type mice. Accordingly, pretreatment of striatal slices with the caspase-3 activator α-(Trichloromethyl)-4-pyridineethanol (PETCM) rescues a physiological LTD in PINK1 knockout mice. Furthermore, the inhibition of caspase-3 prevents the amphetamine-induced rescue of LTD in the same model. Our data support a hormesis-based double role of caspase-3; when massively activated, it induces apoptosis, while at lower level of activation, it modulates physiological phenomena, like the expression of corticostriatal LTD. Exploring the non-apoptotic activation of caspase-3 may contribute to clarify the mechanisms involved in synaptic failure in PD, as well as in view of new potential pharmacological targets.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Proteínas Quinasas / Caspasa 3 Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2019 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Proteínas Quinasas / Caspasa 3 Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2019 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza