Gokhale A, Vrailas-Mortimer A, Larimore J, Comstra HS, Zlatic SA, Werner E, Manvich DF, Iuvone PM, Weinshenker D, Faundez V. Neuronal copper homeostasis susceptibility by genetic defects in dysbindin, a schizophrenia susceptibility factor. Hum Mol Genet. 2015 Oct 1;24(19):5512-23. PMID: 26199316; PMCID: PMC4572075.
From the abstract: "Environmental factors and susceptible genomes interact to determine the risk of neurodevelopmental disorders. ... Here we focus on the schizophrenia susceptibility gene DTNBP1 and its product dysbindin, a subunit of the BLOC-1 complex, and describe a neuronal pathway modulating copper metabolism via ATP7A. ... Dysbindin/BLOC-1 loss-of-function alleles do not affect cell and tissue copper content, yet they alter the susceptibility to toxic copper challenges in both mammalian cells and Drosophila. Our results demonstrate that perturbations downstream of the schizophrenia susceptibility gene DTNBP1 confer susceptibility to copper, a metal that in excess is a neurotoxin and whose depletion constitutes a micronutrient deficiency."
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