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The Role of Arrestins in the Neuroprotective Effects of Antidepressant Drugs

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Melatonin, Neuroprotective Agents and Antidepressant Therapy

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Abstract

Latest hypotheses supported by extensive data assign the pathophysiological basis of major depression to impaired neuroplasticity that is restored by antidepressant-increased neurogenesis and gliogenesis. Here we provide an overview of recent advances concerning the major role played by beta-arrestins in the regulation of the neuroprotective processes underlying the pathophysiology of mood disorders and the mechanism of action of antidepressant drugs. Beta-arrestins are multifunctional regulatory proteins involved in a myriad of essential cellular processes that impair G protein-coupled signaling pathways and at the same time promote numerous other cellular signals including a role as nuclear scaffolds. Beta-arrestins play keys roles in cellular responses to growth factors through various receptor signaling pathways, either G protein dependent or G protein independent. Whether the outcome of beta-arrestin-regulated signaling is pro-survival or proapoptotic depends on the specific configuration of the signaling system in which they act. We highlight recent findings suggesting the hypothesis that beta-arrestins might be the molecular targets for antidepressant action that mediate antidepressant antiapoptotic, neurotrophic, and neuroprotective therapeutic effects.

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Abbreviations

AP-2:

Adaptor protein-2

BAD:

Bcl-2-associated death promoter homologue

Bcl-2:

B cell lymphoma 2 apoptosis regulator

BDNF:

Brain-derived neurotrophic factor

CREB:

cAMP response element-binding protein

ERK1/2:

Extracellular signal-regulated kinase

GDNF:

Glial-derived neurotrophic factor

GPCR:

G protein-coupled receptor

GRK:

G protein-coupled receptor kinase

MAPK:

Mitogen-activated protein kinase

NT:

Neurotrophin

Trk:

Tyrosine kinase

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Authors and Affiliations

  1. Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheba, Israel

    Sofia Avissar

  2. Department of Clinical Biochemistry and Pharmacology, Ben Gurion University of the Negev, Beersheba, Israel

    Moran Golan, Valeria Feinshtein, Siyona Kolatkar & Doron Fux

  3. Division of Psychiatry, Ben Gurion University of the Negev and Barzilai Medical Center, Beersheba, Israel

    Gabriel Schreiber

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  1. Sofia Avissar
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  2. Moran Golan
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  3. Valeria Feinshtein
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  4. Siyona Kolatkar
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  5. Doron Fux
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  6. Gabriel Schreiber
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Correspondence to Sofia Avissar .

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Editors and Affiliations

  1. Vice-Rectorate for Research and Sci, Camilo José Cela University Vice-Rectorate for Research and Sci, Madrid, Spain

    Francisco López-Muñoz

  2. International Medical Sciences Research Study Center, Sri Sathya Sai Medical Educational & Research Foundation, Coimbatore, India

    Venkataramanujam Srinivasan

  3. Department of Neurosciences and Ima, University of Chieti Department of Neurosciences and Ima, Italy, Italy

    Domenico de Berardis

  4. Department of Biomedical Sciences (Pharmacology Area), University of Alcalá, Madrid, Spain

    Cecilio Álamo

  5. Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan

    Takahiro A. Kato

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Avissar, S., Golan, M., Feinshtein, V., Kolatkar, S., Fux, D., Schreiber, G. (2016). The Role of Arrestins in the Neuroprotective Effects of Antidepressant Drugs. In: López-Muñoz, F., Srinivasan, V., de Berardis, D., Álamo, C., Kato, T. (eds) Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2803-5_46

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