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Neurodevelopmental Disorders: Functional Role of Ambra1 in Autism and Schizophrenia

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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.

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Funding

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).

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  1. Livia La Barbera and Francescangelo Vedele contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Neurosciences, Department of Experimental Neurosciences, IRCCS Santa Lucia Foundation, Rome, Italy

    Livia La Barbera, Francescangelo Vedele, Annalisa Nobili, Marcello D’Amelio & Paraskevi Krashia

  2. Department of Systems Medicine, University of Rome ‘Tor Vergata’, Rome, Italy

    Livia La Barbera, Francescangelo Vedele & Paraskevi Krashia

  3. Unit of Molecular Neurosciences, Department of Medicine, University Campus-Biomedico, Rome, Italy

    Annalisa Nobili & Marcello D’Amelio

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  1. Livia La Barbera
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La Barbera, L., Vedele, F., Nobili, A. et al. Neurodevelopmental Disorders: Functional Role of Ambra1 in Autism and Schizophrenia. Mol Neurobiol 56, 6716–6724 (2019). https://doi.org/10.1007/s12035-019-1557-7

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