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Na+ leak-current channel (NALCN) at the junction of motor and neuropsychiatric symptoms in Parkinson’s disease

  • Psychiatry and Preclinical Psychiatric Studies - Review Article
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Abstract

Parkinson’s disease (PD) is a debilitating movement disorder often accompanied by neuropsychiatric symptoms that stem from the loss of dopaminergic function in the basal ganglia and altered neurotransmission more generally. Akinesia, postural instability, tremors and frozen gait constitute the major motor disturbances, whereas neuropsychiatric symptoms include altered circadian rhythms, disordered sleep, depression, psychosis and cognitive impairment. Evidence is emerging that the motor and neuropsychiatric symptoms may share etiologic factors. Calcium/ion channels (CACNA1C, NALCN), synaptic proteins (SYNJ1) and neuronal RNA-binding proteins (RBFOX1) are among the risk genes that are common to PD and various psychiatric disorders. The Na+ leak-current channel (NALCN) is the focus of this review because it has been implicated in dystonia, regulation of movement, cognitive impairment, sleep and circadian rhythms. It regulates the resting membrane potential in neurons, mediates pace-making activity, participates in synaptic vesicle recycling and is functionally co-localized to the endoplasmic reticulum (ER)—several of the major processes adversely affected in PD. Here, we summarize the literature on mechanisms and pathways that connect the motor and neuropsychiatric symptoms of PD with a focus on recurring relationships to the NALCN. It is hoped that the various connections outlined here will stimulate further discussion, suggest additional areas for exploration and ultimately inspire novel treatment strategies.

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Acknowledgements

The authors would like to thank the Department of Psychiatry and Behavioral Medicine at LSU Health Shreveport for support and Dr. Natali Chanaday for helpful comments and suggestions about the paper. In addition, we greatly appreciate two anonymous reviewers whose insightful feedback helped to improve the manuscript.

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The research was not supported by outside funding.

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  1. Department of Pharmacology, Vanderbilt University, Nashville, TN, 37232, USA

    Merve Kasap

  2. Departments of Psychiatry and Pharmacology, Toxicology and Neuroscience, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA, 71130, USA

    Donard S. Dwyer

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  1. Merve Kasap
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MK and DSD both conceived of the ideas contained in the article and contributed to writing and editing of the manuscript.

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Correspondence to Donard S. Dwyer.

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Kasap, M., Dwyer, D.S. Na+ leak-current channel (NALCN) at the junction of motor and neuropsychiatric symptoms in Parkinson’s disease. J Neural Transm 128, 749–762 (2021). https://doi.org/10.1007/s00702-021-02348-6

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