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Updated: Mar 16, 2026
Targeted Neuronal Injury for the Non-Invasive Disconnection of Brain Circuitry
Published on: September 27, 2020
Rescuing neuronal cell death by RAIDD- and PIDD- derived peptides and its implications for therapeutic intervention
Tae-Ho Jang1, In-Hye Lim2, Chang Min Kim1
1School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 38541, South Korea.
Abstract:
Caspase-2 is known to be involved in oxidative-stress mediated neuronal cell death. In this study, we demonstrated that rotenone-induced neuronal cell death is mediated by caspase-2 activation via PIDDosome formation. Our newly designed TAT-fused peptides, which contains wild-type helix number3 (H3) from RAIDD and PIDD, blocked the PIDDosome formation in vitro. Furthermore, peptides inhibited rotenone-induced caspase-2-dependent apoptosis in neuronal cells. These results suggest that PIDD- or RAIDD-targeted peptides might be effective at protecting against rotenone-induced neurotoxicity. Our peptides are novel neuronal cell apoptosis inhibitors that might serve as a prototype for development of drugs for the treatment of neurodegenerative diseases.
Insights
Novel peptides targeting PIDDosome formation inhibit caspase-2 activation, offering a potential therapeutic strategy against rotenone-induced neurotoxicity and neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Caspase-2 activation is implicated in oxidative-stress-induced neuronal cell death.
- PIDDosome formation is a key pathway in caspase-2 activation.
Purpose of the Study:
- To investigate the role of PIDDosome formation in rotenone-induced neuronal cell death.
- To develop and evaluate novel peptides as inhibitors of PIDDosome formation and caspase-2 activation.
Main Methods:
- Utilized rotenone to induce neurotoxicity in neuronal cells.
- Designed and synthesized TAT-fused peptides targeting RAIDD and PIDD proteins.
- Assessed PIDDosome formation inhibition in vitro.
- Evaluated the effect of peptides on caspase-2-dependent apoptosis.
Main Results:
- Rotenone-induced neuronal cell death was confirmed to be mediated by caspase-2 activation via PIDDosome formation.
- TAT-fused peptides effectively blocked PIDDosome formation in vitro.
- These peptides inhibited rotenone-induced apoptosis in neuronal cells.
Conclusions:
- Targeting PIDDosome formation with peptides offers a promising approach to counteract rotenone-induced neurotoxicity.
- The developed peptides are novel inhibitors of neuronal cell apoptosis and may serve as drug prototypes for neurodegenerative diseases.
