Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/18996
Title: DEPDC5 as a potential therapeutic target for epilepsy.
Austin Authors: Myers, Kenneth A;Scheffer, Ingrid E 
Affiliation: Epilepsy Research Centre, Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, Flemington, Victoria, Australia
Issue Date: Jun-2017
metadata.dc.date: 2017-04-13
Publication information: Expert opinion on therapeutic targets 2017; 21(6): 591-600
Abstract: Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome with epilepsy, however GATOR1 gene mutations have recently been shown to cause lesional and non-lesional focal epilepsy. Areas covered: This review summarizes the mTOR pathway, including regulators and downstream effectors, emphasizing recent developments in the understanding of the complex role of the GATOR1 complex. We review the epilepsy types associated with mTOR overactivity, including tuberous sclerosis, polyhydramnios megalencephaly symptomatic epilepsy, cortical dysplasia, non-lesional focal epilepsy and post-traumatic epilepsy. Currently available mTOR inhibitors are discussed, primarily rapamycin analogs and ATP competitive mTOR inhibitors. Expert opinion: DEPDC5 is an attractive therapeutic target in focal epilepsy, as effects of DEPDC5 agonists would likely be anti-epileptogenic and more selective than currently available mTOR inhibitors. Therapeutic effects might be synergistic with certain existing dietary therapies, including the ketogenic diet.
URI: http://ahro.austin.org.au/austinjspui/handle/1/18996
DOI: 10.1080/14728222.2017.1316715
ORCID: 0000-0002-2311-2174
PubMed URL: 28406046
Type: Journal Article
Subjects: DEPDC5
GATOR1
NPRL2
NPRL3
cortical dysplasia
focal epilepsy
mechanistic target of rapamycin
rapamycin
tuberous sclerosis
Appears in Collections:Journal articles

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