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Author Notes:

Correspondence: Christina Gross and Gary J. Bassell, Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA e-mail: gbassel@emory.edu; cgross3@emory.edu

The authors apologize to all colleagues whose work on related topics was not discussed here due to the concise format of this Mini Review.

The authors are co-inventors on patent application PCT/US2010/055387, which suggests the use of (1) PI3K antagonists as a therapeutic treatment for fragile X syndrome and other autism spectrum disorders and (2) PI3K activity as a biomarker for these diseases.

Subjects:

Research Funding:

This work was supported by a Pilot Grant from the Simons Foundation (SFARI #237324 to GJB and CG) and a NARSAD Distinguished Investigator Grant from the Brain and Behavior Research Foundation (to GJB).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • PI3K signaling
  • neuronal signal transduction
  • autism
  • epilepsy
  • schizophrenia
  • LONG-TERM POTENTIATION
  • PHOSPHOINOSITIDE 3-KINASE FAMILY
  • AUTISM SPECTRUM DISORDERS
  • FRAGILE-X-SYNDROME
  • PHOSPHATIDYLINOSITOL 3-KINASE
  • SIGNALING PATHWAY
  • ALZHEIMERS-DISEASE
  • THERAPEUTIC STRATEGIES
  • HIPPOCAMPAL-NEURONS
  • INTRANASAL INSULIN

Neuron-specific regulation of class I PI3K catalytic subunits and their dysfunction in brain disorders

Tools:

Journal Title:

Frontiers in Molecular Neuroscience

Volume:

Volume 7, Number FEB

Publisher:

, Pages 12-12

Type of Work:

Article | Final Publisher PDF

Abstract:

The phosphoinositide 3-kinase (PI3K) complex plays important roles in virtually all cells of the body. The enzymatic activity of PI3K to phosphorylate phosphoinositides in the membrane is mediated by a group of catalytic and regulatory subunits. Among those, the class I catalytic subunits, p110a, p1103, p110y, and p1108, have recently drawn attention in the neuroscience field due to their specific dysregulation in diverse brain disorders. While in non-neuronal cells these catalytic subunits may have partially redundant functions, there is increasing evidence that in neurons their roles are more specialized, and confined to distinct receptor-dependent pathways.This review will summarize the emerging role of class I PI3K catalytic subunits in neurotransmitter-regulated neuronal signaling, and their dysfunction in a variety of neurological diseases, including fragile X syndrome, schizophrenia, and epilepsy. We will discuss recent literature describing the use of PI3K subunit-selective inhibitors to rescue brain disease-associated phenotypes in in vitro and animal models. These studies give rise to the exciting prospect that these drugs, originally designed for cancer treatment, may be repurposed as therapeutic drugs for brain disorders in the future.

Copyright information:

© 2014 Gross and Bassell.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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