Transthyretin

Herbert, Joseph; Wilcox, Josiah N.; Pham, Kim-Thu C.; Fremeau, Robert T.; Zeviani, Massimo; Dwork, Andrew J.; Soprano, Dianne Robert; Makover, Adina; Goodman, DeWitt S.; Zimmerman, Earl A.; Roberts, James L.; Schon, Eric A.

doi:10.1212/wnl.36.7.900

Cited by 306 publications

(174 citation statements)

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“…The researchers reported that the diet among the Ibadan community consists mainly of red palm oil and yams (Hendrie as quoted in The New York Times, February 14, 2001). This diet, high in provitamin A (100, 101), should maximize the levels of retinoid available for adequate storage in target tissues (37) and transport to brain by APOE (53) and other retinoid transporters, e.g., apolipoprotein D (54) and TTR (60). Consistent with this hypothesis, APOE4 is not a risk factor for AD in Ibadan (99).…”

Section: Epidemiologic Findings Relating Retinoid To Admentioning

confidence: 87%

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Evidence for defective retinoid transport and function in late onset Alzheimer's disease

Goodman¹,

Pardee²

2003

Proc. Natl. Acad. Sci. U.S.A.

161

122

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The hypothesis of this article is that late onset Alzheimer's disease (AD) is influenced by the availability in brain of retinoic acid (RA), the final product of the vitamin A (retinoid) metabolic cascade. Genetic, metabolic, and environmental͞dietary evidence is cited supporting this hypothesis. Significant genetic linkages to AD are demonstrated for markers close to four of the six RA receptors, RA receptor G at 12q13, retinoid X receptor B at 6p21.3, retinoid X receptor G at 1q21, and RA receptor A at 17q21. Three of the four retinol-binding proteins at 3q23 and 10q23 and the RA-degrading cytochrome P450 enzymes at 10q23 and 2p13 map to AD linkages. Synthesis of the evidence supports retinoid hypofunction and impaired transport as contributing factors. These findings suggest testable experiments to determine whether increasing the availability of retinoid in brain, possibly through pharmacologic targeting of the RA receptors and the cytochrome P450 RAinactivating enzymes, can prevent or decrease amyloid plaque formation.

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Section: Epidemiologic Findings Relating Retinoid To Admentioning

confidence: 87%

“…TTR is the major carrier of retinol bound to RBP from liver stores through plasma to target tissues. Both RBP alone and complexed with TTR can transport retinoid across the choroid plexus (4,60). RBP and TTR are produced in the fourth ventricle of the brain and are abundant in cerebrospinal fluid (61).…”

Section: Functions Of Retinoid-related Genesmentioning

confidence: 99%

Evidence for defective retinoid transport and function in late onset Alzheimer's disease

Goodman¹,

Pardee²

2003

Proc. Natl. Acad. Sci. U.S.A.

161

122

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“…Unlike plasma TTR, which is derived primarily from the liver, brain TTR is exclusively produced, secreted, and regulated by the choroid plexus (13)(14)(15). The importance of TTR in CNS development is evidenced by the fact that it is present in very high concentration during prenatal and early postnatal life (16).…”

Section: Neurotoxicities Due To Altered Barrier Functions: Aluminum Amentioning

confidence: 99%

Neurotoxicology of the Brain Barrier System: New Implications

Zheng

2001

Journal of Toxicology: Clinical Toxicology

100

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The concept of a barrier system in the brain has existed for nearly a century. The barrier that separates the blood from the cerebral interstitial fluid is defined as the blood-brain barrier, while the one that discontinues the circulation between the blood and cerebrospinal fluid is named the blood-cerebrospinal fluid barrier. Evidence in the past decades suggests that brain barriers are subject to toxic insults from neurotoxic chemicals circulating in blood. The aging process and some disease states render barriers more vulnerable to insults arising inside and outside the barriers. The implication of brain barriers in certain neurodegenerative diseases is compelling, although the contribution of chemical-induced barrier dysfunction in the etiology of any of these disorders remains poorly understood. This review examines what is currently understood about brain barrier systems in central nervous system disorders by focusing on chemical-induced neurotoxicities including those associated with nitrobenzenes, N-methyl-D-aspartate, cyclosporin A, pyridostigmine bromide, aluminum, lead, manganese, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and 3-nitropropionic acid. Contemporary research questions arising from this growing understanding show enormous promises for brain researchers, toxicologists, and clinicians.

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“…Human transthyretin binds thyroxine about 10 times more strongly than triiodothyronine (for review see Robbins and Edelhoch, 1986). Transthyretin is expressed by cells involved in maintaining protein homeostasis in extracellular compartments, such as the hepatocytes in the liver and the ependymal cells of the choroid plexus (Stauder et al, 1986;Herbert et al, 1986). In evolution, the initiation of transthyretin gene expression in the choroid plexus preceded that in the liver by about 2X10* years .…”

mentioning

confidence: 99%

Evolution of Transthyretin in Marsupials

Duan

Richardson

Babon

et al. 1995

European Journal of Biochemistry

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The evolution of the expression and the structure of the gene for transthyretin, a thyroxine-binding plasma protein formerly called prealbumin, was studied in three marsupial species : the South American polyprotodont Monodelphis domestica, the Australian polyprotodont Sminthopsis macroura and the Australian diprotodont Petaurus breviceps. The transthyretin gene was found to be expressed in the choroid plexus of all three species. In liver it was expressed in P. breviceps and in M. domestica, but not in S.macroura. This, together with previous studies [Richardson, S. J., Bradley, A. J., Duan, W., Wettenhall, R. E. H., Harms, P. J., Babon, J. J., Southwell, B. R., Nicol, S., Donnellan, S. C. & Schreiber, G. (1994) Am. .I. Physiol. 266, R1359 -R1370], suggests the independent evolution of transthyretin synthesis in the liver of the American Polyprotodonta and the Australian Diprotodonta.The results obtained from cloning and sequencing of the cDNA for transthyretin from the three species suggested that, in the evolution of the structure of transthyretin in vertebrates, marsupial transthyretin structures are intermediate between birdreptile and eutherian transthyretin structures. In marsupials, as in birds and reptiles, a hydrophobic tripeptide beginning with valine and ending with histidine was found in transthyretin at a position which has been identified in eutherians as the border between exon 1 and intron 1. In humans, rats and mice, the nine nucleotides, coding for this tripeptide in marsupials/reptiles/ birds, are found at the 5' end of intron 1. They are no longer present in mature transthyretin mRNA. This results in a change in character of the N-termini of the subunits of transthyretin from hydrophobic to hydrophilic. This change might affect the accessibility of the thyroxine-binding site in the central channel of tr,ansthyretin, since, at least in humans, the N-termini of the subunits of transthyretin are located in the vicinity of the channel entrance [Hamilton,

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Transthyretin

Cited by 306 publications

References 0 publications

Evidence for defective retinoid transport and function in late onset Alzheimer's disease

Evidence for defective retinoid transport and function in late onset Alzheimer's disease

Neurotoxicology of the Brain Barrier System: New Implications

Evolution of Transthyretin in Marsupials

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