Neuronal α 2 δ proteins and brain disorders

α δ proteins are membrane-anchored extracellular glycoproteins which are abundantly expressed in the brain and the peripheral nervous system. They serve as regulatory subunits of voltage-gated calcium channels and, particularly in nerve cells, regulate presynaptic and postsynaptic functions independ...

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Bibliographic Details
Published inPflügers Archiv Vol. 472; no. 7; p. 845
Main Authors Ablinger, Cornelia, Geisler, Stefanie M, Stanika, Ruslan I, Klein, Christian T, Obermair, Gerald J
Format Journal Article
LanguageEnglish
Published Germany 01.07.2020
Subjects
Animals
Brain Diseases - genetics
Brain Diseases - pathology
Calcium Channels - genetics
Epilepsy - genetics
Epilepsy - pathology
Humans
Membrane Glycoproteins - genetics
Neurons - pathology
Protein Isoforms - genetics
Autism
CACNA2D1–4
Epilepsy
Schizophrenia
Neurological disease
Synapses
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Summary:α δ proteins are membrane-anchored extracellular glycoproteins which are abundantly expressed in the brain and the peripheral nervous system. They serve as regulatory subunits of voltage-gated calcium channels and, particularly in nerve cells, regulate presynaptic and postsynaptic functions independently from their role as channel subunits. α δ proteins are the targets of the widely prescribed anti-epileptic and anti-allodynic drugs gabapentin and pregabalin, particularly for the treatment of neuropathic pain conditions. Recently, the human genes (CACNA2D1-4) encoding for the four known α δ proteins (isoforms α δ-1 to α δ-4) have been linked to a large variety of neurological and neuropsychiatric disorders including epilepsy, autism spectrum disorders, bipolar disorders, schizophrenia, and depressive disorders. Here, we provide an overview of the hitherto identified disease associations of all known α δ genes, hypothesize on the pathophysiological mechanisms considering their known physiological roles, and discuss the most immanent future research questions. Elucidating their specific physiological and pathophysiological mechanisms may open the way for developing entirely novel therapeutic paradigms for treating brain disorders.
ISSN:1432-2013