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Cultivation of Human Neural Progenitor Cells in a 3-dimensional Self-assembling Peptide Hydrogel
Published on: January 11, 2012
Use of cell-permeable peptides to prevent neuronal degeneration
Tiziana Borsello1, Christophe Bonny
1IBCM, University of Lausanne, Lausanne, Switzerland. Tiziana.Borsello@ibcm.unil.ch
Abstract:
The loss of neurons is a hallmark of neurodegenerative disorders and evidence suggests that this occurs through an apoptotic mechanism. Following an insult, neuronal cells activate signal transduction pathways that lead to cell death and the establishment of the pathological state. The mechanisms underlying the cell-death response involve protein kinases, which phosphorylate many substrates and culminate in changes in gene expression. Traditionally, attempts at blocking such signaling targeted the phosphorylation of the substrates. However, preventing the interaction between two proteins using specific peptides might block the function of key mediators in signaling cascades. A cell-permeable peptide designed specifically to inhibit c-Jun N-terminal kinase action proved successful in in vivo models of neuronal degeneration following ischemia. Here, the recent findings that highlight the potential of this approach for therapeutic application are reviewed.
Insights
Targeting protein interactions with specific peptides can block cell death pathways in neurodegenerative disorders. A peptide inhibiting c-Jun N-terminal kinase shows promise for treating neuronal loss after ischemia.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Neuronal loss is a key feature of neurodegenerative diseases, often involving apoptosis.
- Signal transduction pathways activated by cellular insults lead to neuronal death and disease pathology.
- Protein kinases play a crucial role in mediating cell-death signaling cascades.
Purpose of the Study:
- To review recent findings on therapeutic strategies targeting protein interactions in neurodegenerative disorders.
- To highlight the potential of peptide inhibitors in blocking key signaling mediators.
- To discuss the application of inhibiting c-Jun N-terminal kinase for neuronal protection.
Main Methods:
- Review of recent scientific literature on neurodegeneration and apoptosis.
- Analysis of signaling pathways involving protein kinases and their substrates.
- Evaluation of studies using cell-permeable peptides to inhibit specific protein interactions, particularly c-Jun N-terminal kinase.
Main Results:
- Blocking protein-protein interactions offers an alternative to targeting substrate phosphorylation in cell-death pathways.
- A cell-permeable peptide inhibitor of c-Jun N-terminal kinase demonstrated efficacy in preclinical models.
- This approach showed success in preventing neuronal degeneration following ischemic events.
Conclusions:
- Interfering with specific protein interactions, such as those involving c-Jun N-terminal kinase, presents a promising therapeutic avenue.
- Peptide-based inhibitors can effectively block critical signaling cascades implicated in neuronal death.
- This strategy holds significant potential for developing novel treatments for neurodegenerative conditions and stroke.
