ABSTRACT
Although vitamin E has been recognized as a critical micronutrient to neuronal health for more than half a century, vitamin E transport and regulation in the brain remain a mystery. Currently, the majority of what is known about vitamin E transport has been delineated in the liver. However, clues from the pathogenesis of neurological-related vitamin E deficient diseases point to compromised neuronal integrity and function, underlining the critical need to understand vitamin E regulation in the CNS. Additionally, most of the same molecular players involved in vitamin E transport in the liver are also found in CNS, including sterol SRB1, TTP, and ABCA/ABCG, suggesting similar intracellular pathways between these organ systems. Finally, based on chemical similarities, intracellular CNS shuttling of vitamin E likely resembles cholesterol's use of ApoE particles. Utilizing this information, this review will address what is currently known about trafficking vitamin E across the blood brain barrier in order to ensure an adequate supply of the essential nutrient to the brain. Although debatable, the health of the brain in relation to vitamin E levels has been demonstrated, most notably in oxidative stress-related conditions such as ataxias, Alzheimer's disease, and Parkinson's disease. Future vitamin E research is vital in understanding how the regulation of the vitamin can aid in the prevention, treatment, and curing of neurological diseases. © 2018 IUBMB Life, 71(4):424-429, 2019.
Subject(s)
Central Nervous System/metabolism , Vitamin E Deficiency/etiology , Vitamin E/pharmacokinetics , Animals , Biological Transport , Blood-Brain Barrier/metabolism , Brain/metabolism , Carrier Proteins/metabolism , Central Nervous System/drug effects , Humans , Mice , Vitamin E/metabolism , alpha-Tocopherol/metabolismABSTRACT
For the last two decades, it has been hotly debated whether vitamin E-the major lipid-soluble antioxidant, which functions to maintain neurological integrity-is efficacious as a therapy for Alzheimer's disease. Several factors key to the debate, include (1) which of the eight naturally-occurring vitamin E forms should be used; (2) how combination treatments affect vitamin E efficacy; and (3) safety concerns that most-recently resurfaced after the results of the Selenium and vitamin E Cancer prevention trial SELECT prostate cancer trial. However, with the advent of new genetic technologies and identifications of vitamin E-modulating single nucleotide polymorphisms (SNPs), we propose that clinical trials addressing the question "Is vitamin E an effective treatment for Alzheimer's disease" should consider a more focused and personalized medicine approach to designing experiments. An individual's naturally-occurring SNP variants may indeed influence vitamin E's therapeutic effect on Alzheimer's disease.
ABSTRACT
Alpha-tocopherol (vitamin E) is a plant-derived antioxidant that is essential for human health. Studies with humans and with animal models of vitamin E deficiency established the critical roles of the vitamin in protecting the central nervous system, and especially the cerebellum, from oxidative damage and motor coordination deficits. We review here the established roles of vitamin E in protecting cerebellar functions, as well as emerging data demonstrating the critical roles of alpha-tocopherol in preserving learning, memory and emotive responses. We also discuss the importance of vitamin E adequacy in seemingly unrelated neurological disorders.
Subject(s)
Neurodegenerative Diseases/metabolism , Vitamin E/metabolism , Animals , Cognition/physiology , Humans , Neurodegenerative Diseases/psychology , Vitamin E/chemistry , Vitamin E Deficiency/metabolism , Vitamin E Deficiency/psychologyABSTRACT
Regulation of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA levels is not well understood. Mouse Cftr mRNA shows strain-dependent expression differences that cannot be fully explained by variation at non-Cftr loci. Differences in tracheal and colonic expression appear to be due predominantly to elements linked to Cftr. Fifteen single nucleotide sequence variations were found within 1.4 kb 5' to the translation start site between the inbred lines A/J, C57BL/6J and 129/SvJ. In addition, 129/SvJ carries a 100 bp deletion relative to the other two strains. These variants were investigated by sequentially deleting 5' regions and measuring luciferase reporter activity from transfected, mouse epithelial cell lines derived from pancreatic duct, renal collecting duct, salivary gland and trachea. These assays identified a region between -524 and -834 in the C57BL/6J promoter, but not in A/J or 129/SvJ, capable of repressing expression. Sequence analysis and gel mobility shift assays suggest that the transcription factor MZF is involved in the strain-dependent effect. It was also apparent that several reporter constructs displayed expression differences between cell lines, possibly indicating the presence of tissue-specific elements.
