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Molecular Brain Jun 2020The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum...
OBJECTIVES
The present review systematically summarized existing publications regarding the genetic associations between voltage-gated calcium channels (VGCCs) and autism spectrum disorder (ASD).
METHODS
A comprehensive literature search was conducted to gather pertinent studies in three online databases. Two authors independently screened the included records based on the selection criteria. Discrepancies in each step were settled through discussions.
RESULTS
From 1163 resulting searched articles, 28 were identified for inclusion. The most prominent among the VGCCs variants found in ASD were those falling within loci encoding the α subunits, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1F, CACNA1G, CACNA1H, and CACNA1I as well as those of their accessory subunits CACNB2, CACNA2D3, and CACNA2D4. Two signaling pathways, the IP3-Ca pathway and the MAPK pathway, were identified as scaffolds that united genetic lesions into a consensus etiology of ASD.
CONCLUSIONS
Evidence generated from this review supports the role of VGCC genetic variants in the pathogenesis of ASD, making it a promising therapeutic target. Future research should focus on the specific mechanism that connects VGCC genetic variants to the complex ASD phenotype.
Topics: Autism Spectrum Disorder; Calcium Channels; Calcium Signaling; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Protein Subunits
PubMed: 32571372
DOI: 10.1186/s13041-020-00634-0 -
International Journal of Molecular... Dec 2021Pesticides of different chemical classes exert their toxic effects on the nervous system by acting on the different regulatory mechanisms of calcium (Ca) homeostasis....
Pesticides of different chemical classes exert their toxic effects on the nervous system by acting on the different regulatory mechanisms of calcium (Ca) homeostasis. Pesticides have been shown to alter Ca homeostasis, mainly by increasing its intracellular concentration above physiological levels. The pesticide-induced Ca overload occurs through two main mechanisms: the entry of Ca from the extracellular medium through the different types of Ca channels present in the plasma membrane or its release into the cytoplasm from intracellular stocks, mainly from the endoplasmic reticulum. It has also been observed that intracellular increases in the Ca concentrations are maintained over time, because pesticides inhibit the enzymes involved in reducing its levels. Thus, the alteration of Ca levels can lead to the activation of various signaling pathways that generate oxidative stress, neuroinflammation and, finally, neuronal death. In this review, we also discuss some proposed strategies to counteract the detrimental effects of pesticides on Ca homeostasis.
Topics: Animals; Calcium; Calcium Channels; Calcium Signaling; Calcium, Dietary; Cell Membrane; Homeostasis; Humans; Neuroinflammatory Diseases; Neurotoxicity Syndromes; Oxidative Stress; Pesticides
PubMed: 34948173
DOI: 10.3390/ijms222413376 -
Medical Oncology (Northwood, London,... Oct 2018Metabolic alterations in the tumor microenvironment have a complex effect on cancer progression. Extracellular acidity is a consequence of metabolic switch in cancer and...
Metabolic alterations in the tumor microenvironment have a complex effect on cancer progression. Extracellular acidity is a consequence of metabolic switch in cancer and results in cell phenotypes with higher resistance to chemotherapeutics. However, mechanisms underlying the relationship between the extracellular acidity and chemoresistance are not clearly understood. This systematic review was carried out by searching the databases PubMed and EMBASE using the keywords "cancer" and "acidosis" or "acidic" and "chemoresistance" or "drug resistance." In vitro and in vivo studies that evaluated the effects of acidification of the tumor microenvironment on chemotherapeutic treatments were included. Literature reviews, letters to the editor, and articles that were not published in English were excluded. The search resulted in a total of 352 articles. After discarding 75 duplicate references, 277 articles were analyzed by sequentially reading through their titles, abstracts, and finally full-text. A total of 14 articles was selected. Acidification of the tumor microenvironment can trigger resistance through different mechanisms, such as increase in drug efflux transporters, inhibition of proton pumps, induction of the unfolded protein response (UPR), and cellular autophagy.
Topics: Animals; Antineoplastic Agents; Autophagy; Drug Resistance, Neoplasm; Humans; Hydrogen-Ion Concentration; Membrane Transport Proteins; Neoplasms; Tumor Microenvironment; Unfolded Protein Response
PubMed: 30377828
DOI: 10.1007/s12032-018-1214-4 -
Drug Delivery Nov 2018To achieve sufficient blood-brain barrier (BBB), penetration is one of the biggest challenges in the development of diagnostic and therapeutic for central nervous system... (Meta-Analysis)
Meta-Analysis
Borneol, a messenger agent, improves central nervous system drug delivery through enhancing blood-brain barrier permeability: a preclinical systematic review and meta-analysis.
To achieve sufficient blood-brain barrier (BBB), penetration is one of the biggest challenges in the development of diagnostic and therapeutic for central nervous system (CNS) disorders. Here, we conducted a systematic review and meta-analysis to assess the preclinical evidence and possible mechanisms of borneol for improving co-administration of CNS drug delivery in animal models. The electronic literature search was conducted in six databases. Fifty-eight studies with 63 comparisons involved 1137 animals were included. Among 47 studies reporting the assessments of CNS drug concentration, 45 studies showed the significant effects of borneol for improving CNS drug delivery (p<.05), whereas 2 studies showed no difference (p>.05). Nineteen comparisons showed borneol up-regulated BBB permeability (p<.05) using brain EB content (n = 8), Rh 123 content (n = 4), brain imaging agent content (n = 2), brain water content (n = 1) and observing ultrastructure of BBB (n = 4), whereas three studies showed no difference or unclear results. Seven studies reported the safety, in which one study showed borneol was reversible changes in the BBB penetration; six studies showed borneol did not increase co-administration of blood drugs concentration of peripheral tissues (p > .05). Effects of borneol are closely associated with inhibition of efflux protein function, releasement of tight junction protein, increasement of vasodilatory neurotransmitters, and inhibition of active transport by ion channels. In conclusion, borneol is a promising candidate for CNS drug delivery, mainly through mediating a multi-targeted BBB permeability.
Topics: Animals; Blood-Brain Barrier; Camphanes; Central Nervous System Agents; Central Nervous System Diseases; Drug Carriers; Female; Humans; Male; Permeability
PubMed: 30334462
DOI: 10.1080/10717544.2018.1486471