Impaired calcium signalling and neuropsychiatric disorders in Darier disease: An exploratory review

Area of Science:

• Genetics and Molecular Biology
• Neuroscience
• Dermatology

Background:

• Darier disease (DD) is an autosomal dominant skin disorder stemming from mutations in the ATP2A2 gene, impacting cellular calcium regulation (SERCA2).
• Patients with DD exhibit a high incidence of neuropsychiatric disorders, including intellectual disability, bipolar disorder, schizophrenia, and suicidality.
• The pathophysiological links between DD and these neurological conditions remain underexplored.

Purpose of the Study:

• To review literature on neuropsychiatric disorders associated with Darier disease.
• To elucidate the pathophysiological mechanisms connecting DD and neurological conditions.
• To examine potential therapeutic interventions for future development.

Main Methods:

• A comprehensive literature search was conducted using PubMed.
• Keywords included Darier disease, neuropsychiatric disorders, ATP2A2 gene, SERCA2, and related signaling pathways.
• Sixty-one relevant articles published within the last 40 years were included in this review.

Main Results:

• The review synthesizes current knowledge on the association between Darier disease and various neuropsychiatric conditions.
• It highlights the role of impaired calcium homeostasis due to SERCA2 dysfunction in the central nervous system.
• Potential mechanisms involving sphingosine-1-phosphate and P2X7 receptor signaling are discussed.

Conclusions:

• Understanding the link between Darier disease genetics and neuropsychiatric conditions is crucial.
• Further research into the shared pathophysiological pathways can guide the development of targeted therapies.
• This review provides a foundation for investigating novel interventions for DD patients with neurological comorbidities.