Gene & protein in disease最新文献

The D2 dopamine receptor (DRD2) gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the DRD2 Taq A1 allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the DRD2 gene listed in PUBMED. There have been 120 meta-analyses with mixed results. In our opinion, the primary cause of negative reports regarding the association of various DRD2 gene polymorphisms is the inadequate screening of controls, not adequately eliminating many hidden reward deficiency syndrome behaviors. Moreover, pleiotropic effects of DRD2 variants have been identified in neuropsychologic, neurophysiologic, stress response, social stress defeat, maternal deprivation, and gambling disorder, with epigenetic DNA methylation and histone post-translational negative methylation identified as discussed in this article. There are 70 articles listed in PUBMED for DNA methylation and 20 articles listed for histone methylation as of October 19, 2022. For this commentary, we did not denote DNA and/or histone methylation; instead, we provided a brief summary based on behavioral effects. Based on the fact that Blum and Noble characterized the DRD2 Taq A1 allele as a generalized reward gene and not necessarily specific alcoholism, it now behooves the field to find ways to either use effector moieties to edit the neuroepigenetic insults or possibly harness the idea of potentially removing negative mRNA-reduced expression by inducing "dopamine homeostasis."

Chronic prenatal alcohol exposure causes fetal alcohol spectrum disorder (FASD), often associated with impaired placentation and intrauterine growth restriction. Ethanol's inhibition of insulin and insulin-like growth factor Type 1 (IGF-1) signaling compromises trophoblastic cell motility and maternal vascular transformation at the implantation site. Previous studies have demonstrated that dietary soy effectively normalizes placentation and fetal growth in an experimental model of FASD. The studies were extended to better understand the mechanisms underlying soy's beneficial effects. Pregnant Long Evans rats were pair-fed with isocaloric liquid diets containing either 0% or 36% caloric ethanol from gestation day (GD) 6. The protein source in the diets consisted of either casein (standard and control) or soy isolate. On GD19, placentas were harvested to measure mRNA levels corresponding to major components of the insulin/IGF-1 pathway, as well as aspartyl-asparaginyl-β-hydroxylase (ASPH), Notch, and HES, which play critical roles in placentation. Chronic gestational ethanol exposure in rats fed diets containing casein significantly reduced the expression of insulin, insulin receptor, Igf1, IGF-1 receptor (Igf1r), insulin receptor substrate Type 1 (Irs1), Irs2, Asph, and Hes1. In addition, ethanol significantly decreased ASPH protein expression. Dietary soy mitigated most of these effects and further enhanced signaling by upregulating Igf2, Igf2r, Irs1, Irs2, Irs4, Notch, and Hes1 in rats chronically exposed to ethanol relative to corresponding control samples. The protective effects of dietary soy in FASD act at the mRNA level and positively impact pathways imperative for normal placentation and fetal development. Gestational dietary soy may provide an effective means of preventing FASD in vulnerable populations.

Arteriovenous malformations (AVM) are congenital malformations of the cerebral vasculature resulting in pathological shunting of blood through dilated arteries and veins. The most common clinical manifestations of AVM are intracerebral hemorrhage, due to rupture of these lesions as they continue to expand, which can have devastating neurological consequences and residual deficits. The genetic underpinnings of AVM have been explored for their role in the angiogenesis of these lesions in both its sporadic and inherited forms. In recent times, our understanding of the genetic variation involved in the pathogenesis AVM has advanced in both the preclinical and clinical realms. The current review highlights in detail these advancements, namely, the genetic underpinnings of diagnostic testing and profiling of AVM, and the preclinical epigenetic and genetic data on AVM pathogenesis and growth. In addition, we review the current candidate genes implicated in AVM pathogenesis in the literature. Finally, we provide a discussion on the genetic conditions associated with AVM and the advancements in treatment paradigms influenced by the genetic profiles of these lesions.