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Loss of Non-Apoptotic Role of Caspase-3 in the PINK1 Mouse Model of Parkinson's Disease
- Source :
- International Journal of Molecular Sciences, Volume 20, Issue 14, International Journal of Molecular Sciences, Vol 20, Iss 14, p 3407 (2019)
- Publication Year :
- 2019
- Publisher :
- Zenodo, 2019.
-
Abstract
- 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&rsquo<br />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 &alpha<br />(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<br />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.
- Subjects :
- Programmed cell death
caspase-3
Genotype
striatum
Dopamine
Glutamic Acid
Caspase 3
Catalysis
Article
Inorganic Chemistry
lcsh:Chemistry
Mice
Parkinson's disease
PINK1
synaptic plasticity
long-term depression
Tensin
Animals
Physical and Theoretical Chemistry
Long-term depression
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Caspase
Mice, Knockout
Neuronal Plasticity
biology
Dopaminergic Neurons
Long-Term Synaptic Depression
Organic Chemistry
Parkinson Disease
General Medicine
Corpus Striatum
Computer Science Applications
Cell biology
Enzyme Activation
Disease Models, Animal
lcsh:Biology (General)
lcsh:QD1-999
Apoptosis
Synaptic plasticity
Knockout mouse
biology.protein
Parkinson’s disease
Protein Kinases
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences, Volume 20, Issue 14, International Journal of Molecular Sciences, Vol 20, Iss 14, p 3407 (2019)
- Accession number :
- edsair.doi.dedup.....20cb070124e0cf4790ed0f4f769e2fc7
- Full Text :
- https://doi.org/10.5281/zenodo.4433882