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Current Understanding of PDE10A in the Modulation of Basal Ganglia Circuitry

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Book cover Phosphodiesterases: CNS Functions and Diseases

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 17))

Abstract

The basal ganglia are a forebrain network of interconnected nuclei that are involved in action selection, reward circuits and coordinating movement. PDE10A inhibition has been proposed as a novel way to modulate basal ganglia circuitry and to ameliorate symptoms in Huntington’s disease, Parkinson’s disease and Schizophrenia. However, despite encouraging results from pre-clinical models, PDE10A inhibitors failed to show efficacy as an antipsychotic in several clinical trials. PDE10A is expressed in the medium spiny neurons of the striatum and works to limit cyclic nucleotide signaling in response to modulatory neurotransmitters like dopamine. In this chapter, we will review the current literature on PDE10A and discuss how inhibition of PDE10A will result in alterations of the basal ganglia circuitry at the biochemical, physiological and behavioral level.

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Conflict of Interest

Nicholas J. Brandon and Jan-Philip Schülke were both full-time employees and shareholders in AstraZeneca at the time of writing.

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  1. Evotec, Am Klopferspitz 19a, 82152, Martinsried, Germany

    Jan-Philip Schülke

  2. AstraZeneca Neuroscience, Innovative Medicines and Early Development Biotech Unit, Waltham, MA, 02451, USA

    Nicholas J. Brandon

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  1. Jan-Philip Schülke
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  1. Department of Behavioral Medicine and Psychiatry; Department of Physiology and Pharmacology; Institute of Pharmacology, West Virginia University Health Sciences Center; Taishan Medical University, Morgantown; Taian, China, West Virginia, USA

    Han-Ting Zhang

  2. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo The State University of New York, Buffalo, New York, USA

    Ying Xu

  3. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo The State University of New York, Buffalo, New York, USA

    James M. O'Donnell

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Schülke, JP., Brandon, N.J. (2017). Current Understanding of PDE10A in the Modulation of Basal Ganglia Circuitry. In: Zhang, HT., Xu, Y., O'Donnell, J. (eds) Phosphodiesterases: CNS Functions and Diseases. Advances in Neurobiology, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-319-58811-7_2

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