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Molecular Neurobiology

, Volume 56, Issue 10, pp 6716–6724 | Cite as

Neurodevelopmental Disorders: Functional Role of Ambra1 in Autism and Schizophrenia

  • Livia La Barbera
  • Francescangelo Vedele
  • Annalisa Nobili
  • Marcello D’AmelioEmail author
  • Paraskevi KrashiaEmail author
Article

Abstract

The activating molecule in Beclin-1-regulated autophagy (Ambra1) is a highly intrinsically disordered protein best known for its role as a mediator in autophagy, by favoring the formation of autophagosomes. Additional studies have revealed that Ambra1 is able to coordinate cell responses to stress conditions such as starvation, and it actively participates in cell proliferation, cytoskeletal modification, apoptosis, mitochondria removal, and cell cycle downregulation. All these functions highlight the importance of Ambra1 in crucial physiological events, including metabolism, cell death, and cell division. Importantly, Ambra1 is also crucial for proper embryonic development, and its complete absence in knock-out animal models leads to severe brain morphology defects. In line with this, it has recently been implicated in neurodevelopmental disorders affecting humans, particularly autism spectrum disorders and schizophrenia. Here, we discuss the recent links between Ambra1 and neurodevelopment, particularly focusing on its role during the maturation of hippocampal parvalbumin interneurons and its importance for maintaining a proper excitation/inhibition balance in the brain.

Keywords

Ambra1 Autophagy Autism spectrum disorder Schizophrenia Hippocampus Parvalbumin interneuron Excitation/inhibition 

Notes

Funding Information

A.N. was supported by a post-doctoral Fellowship by the Collegio Ghislieri. P.K. was supported by a post-doctoral Fellowship by the Veronesi Foundation. M.D.A. was supported by an Alzheimer Association’s Research Grant (AARG-18-566270).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Molecular Neurosciences, Department of Experimental NeurosciencesIRCCS Santa Lucia FoundationRomeItaly
  2. 2.Department of Systems MedicineUniversity of Rome ‘Tor Vergata’RomeItaly
  3. 3.Unit of Molecular Neurosciences, Department of MedicineUniversity Campus-BiomedicoRomeItaly

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