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DEPDC5 as a potential therapeutic target for epilepsy
Kenneth A Myers1,2, Ingrid E Scheffer1,2,3
1a Epilepsy Research Centre, Department of Medicine , The University of Melbourne, Austin Health , Heidelberg , Victoria , Australia.
Expert Opinion on Therapeutic Targets
|April 14, 2017
Summary
Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) mutations are linked to focal epilepsy. Targeting DEPDC5 may offer a more selective approach to treating mTOR-related epilepsy than current inhibitors.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex, a modulator of mechanistic target of rapamycin (mTOR) activity.
- Disruption of the mTOR pathway is implicated in various forms of epilepsy, including genetic and acquired.
- Mutations in GATOR1 genes, including DEPDC5, have been identified as a cause of focal epilepsy.
Purpose of the Study:
- To review the mechanistic target of rapamycin (mTOR) pathway, its regulators, and downstream effectors.
- To emphasize recent understanding of the GATOR1 complex's role in epilepsy.
- To discuss current mTOR inhibitors and explore DEPDC5 as a potential therapeutic target.
Main Methods:
- Literature review of the mTOR pathway and its relation to epilepsy.
- Analysis of GATOR1 complex function and DEPDC5 mutations.
- Discussion of existing mTOR inhibitors and potential novel therapeutic strategies.
Main Results:
- The mTOR pathway is crucial for cell proliferation and metabolism, with dysregulation linked to epilepsy.
- GATOR1 complex, including DEPDC5, plays a significant role in modulating mTOR activity.
- DEPDC5 mutations are associated with both lesional and non-lesional focal epilepsy.
Conclusions:
- DEPDC5 is a promising therapeutic target for focal epilepsy due to its role in the mTOR pathway.
- Targeting DEPDC5 may offer more selective anti-epileptogenic effects compared to current mTOR inhibitors.
- Therapeutic strategies targeting DEPDC5 could potentially be synergistic with dietary therapies like the ketogenic diet.