schliessen

Filtern

 

Bibliotheken

A Thyroid Hormone–Based Strategy for Correcting the Biochemical Abnormality in X-Linked Adrenoleukodystrophy

Abstract X-linked adrenoleukodystrophy (X-ALD) is a rare, genetic disorder characterized by adrenal insufficiency and central nervous system (CNS) demyelination. All patients with X-ALD have the biochemical abnormality of elevated blood and tissue levels of very long chain fatty acids (VLCFAs), satu... Full description

Journal Title: Endocrinology (Philadelphia) 2017-05-01, Vol.158 (5), p.1328-1338
Main Author: Hartley, Meredith D
Other Authors: Kirkemo, Lisa L , Banerji, Tapasree , Scanlan, Thomas S
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Washington, DC: Endocrine Society
ID: ISSN: 0013-7227
Link: https://www.ncbi.nlm.nih.gov/pubmed/28200172
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5460829
title: A Thyroid Hormone–Based Strategy for Correcting the Biochemical Abnormality in X-Linked Adrenoleukodystrophy
format: Article
creator:
  • Hartley, Meredith D
  • Kirkemo, Lisa L
  • Banerji, Tapasree
  • Scanlan, Thomas S
subjects:
  • Abridged Index Medicus
  • Acetates - administration & dosage
  • Acetates - therapeutic use
  • Adrenoleukodystrophy
  • Adrenoleukodystrophy - blood
  • Adrenoleukodystrophy - drug therapy
  • Adrenoleukodystrophy - genetics
  • Adrenoleukodystrophy - metabolism
  • Animals
  • ATP Binding Cassette Transporter, Sub-Family D
  • ATP Binding Cassette Transporter, Sub-Family D, Member 1
  • ATP-Binding Cassette Transporters - deficiency
  • ATP-Binding Cassette Transporters - genetics
  • ATP-Binding Cassette Transporters - metabolism
  • Biological Transport
  • Blood
  • Brain - metabolism
  • Cell Line
  • Central nervous system
  • Chains
  • Complementation
  • Demyelination
  • Disease
  • Editor's Choice
  • endocrine system
  • endocrine system diseases
  • Fatty acids
  • Fatty Acids - blood
  • Fatty Acids - metabolism
  • Fibroblasts
  • Fish oils
  • Genetic disorders
  • Homology
  • Humans
  • Male
  • Metabolism in Endocrine Health
  • Metabolism in Endocrine Health and Disease
  • Mice
  • Mutation
  • Organs
  • Oxidation
  • Peroxisomes
  • Peroxisomes - metabolism
  • Pharmacology
  • Phenols - administration & dosage
  • Phenols - therapeutic use
  • Receptors, Thyroid Hormone - agonists
  • Special Section
  • Strategy
  • Thyroid
  • Thyroid gland
  • Thyroid Hormones - administration & dosage
  • Thyroid Hormones - metabolism
  • Thyroid Hormones - therapeutic use
  • Transporter
ispartof: Endocrinology (Philadelphia), 2017-05-01, Vol.158 (5), p.1328-1338
description: Abstract X-linked adrenoleukodystrophy (X-ALD) is a rare, genetic disorder characterized by adrenal insufficiency and central nervous system (CNS) demyelination. All patients with X-ALD have the biochemical abnormality of elevated blood and tissue levels of very long chain fatty acids (VLCFAs), saturated fatty acids with 24 to 26 carbons. X-ALD results from loss of function mutations in the gene encoding the peroxisomal transporter ABCD1, which is responsible for uptake of VLCFAs into peroxisomes for degradation by oxidation. One proposed therapeutic strategy for genetic complementation of ABCD1 is pharmacologic upregulation of ABCD2, a gene encoding a homologous peroxisomal transporter. Here, we show that thyroid hormone or sobetirome, a clinical-stage selective thyroid hormone receptor agonist, increases cerebral Abcd2 and lowers VLCFAs in blood, peripheral organs, and brains of mice with defective Abcd1. These results support an approach to treating X-ALD that involves a thyromimetic agent that reactivates VLCFA disposal both in the periphery and the CNS. Thyroid hormone and the thyromimetic sobetirome lower CNS levels of very long chain fatty acids in a mouse model of X-linked adrenoleukodystrophy supporting a therapeutic strategy for X-ALD.
language: eng
source:
identifier: ISSN: 0013-7227
fulltext: no_fulltext
issn:
  • 0013-7227
  • 1945-7170
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.5980144
LOCALfalse
PrimoNMBib
record
control
sourceidproquest_pubme
recordidTN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5460829
sourceformatXML
sourcesystemPC
oup_id10.1210/en.2016-1842
sourcerecordid1969941877
originalsourceidFETCH-LOGICAL-1519t-8e0c8951728595e5cd986d5f0d0883ed3365a945dcdaf649b091f510d1889f450
addsrcrecordideNp1ks1uEzEUhUcIRNPCjjUaiQUsmGJ7_LtBSiMgSJFYUCR2ljO-k3E7sYPHgzQ73qFvyJPgkFDRSl1Zlr97fO7RKYoXGJ1jgtE78OcEYV5hScmjYoYVZZXAAj0uZgjhuhKEiJPidBiu8pVSWj8tTogk-SLIrPDz8rKbYnC2XIa4DR5-_7q5MAPY8muKJsFmKtsQy0WIEZrk_KZMHZQXLjQdbF1j-nK-9nnS9C5NpfPl92rl_HWen9sIPvQwXgc7DSmGXTc9K560ph_g-fE8K759_HC5WFarL58-L-arCjOsUiUBNVKx7FAyxYA1VkluWYsskrIGW9ecmbyobaxpOVVrpHDLMLJYStVShs6K9wfd3bjegm3A52V6vYtua-Kkg3H67ot3nd6En5pRjiRRWWB5EAg78MZFuDNrPSQdrCZcaGYokQKsIKauiZQcK4I5z46JFZjiLPXm6CWGHyMMSW_d0EDfGw9hHDSWXCHOEdmjr-6hV2GMPielseJKUSyFyNTbA9XEMAwR2ltvGOl9JzR4ve-E3nci4y__z-IW_leCDJB7eo1LJrmwj8b1D6m-PgY07h76_28n0R87u83f
sourcetypeOpen Access Repository
isCDItrue
recordtypearticle
pqid1969941877
display
typearticle
titleA Thyroid Hormone–Based Strategy for Correcting the Biochemical Abnormality in X-Linked Adrenoleukodystrophy
creatorHartley, Meredith D ; Kirkemo, Lisa L ; Banerji, Tapasree ; Scanlan, Thomas S
creatorcontribHartley, Meredith D ; Kirkemo, Lisa L ; Banerji, Tapasree ; Scanlan, Thomas S
descriptionAbstract X-linked adrenoleukodystrophy (X-ALD) is a rare, genetic disorder characterized by adrenal insufficiency and central nervous system (CNS) demyelination. All patients with X-ALD have the biochemical abnormality of elevated blood and tissue levels of very long chain fatty acids (VLCFAs), saturated fatty acids with 24 to 26 carbons. X-ALD results from loss of function mutations in the gene encoding the peroxisomal transporter ABCD1, which is responsible for uptake of VLCFAs into peroxisomes for degradation by oxidation. One proposed therapeutic strategy for genetic complementation of ABCD1 is pharmacologic upregulation of ABCD2, a gene encoding a homologous peroxisomal transporter. Here, we show that thyroid hormone or sobetirome, a clinical-stage selective thyroid hormone receptor agonist, increases cerebral Abcd2 and lowers VLCFAs in blood, peripheral organs, and brains of mice with defective Abcd1. These results support an approach to treating X-ALD that involves a thyromimetic agent that reactivates VLCFA disposal both in the periphery and the CNS. Thyroid hormone and the thyromimetic sobetirome lower CNS levels of very long chain fatty acids in a mouse model of X-linked adrenoleukodystrophy supporting a therapeutic strategy for X-ALD.
identifier
0ISSN: 0013-7227
1EISSN: 1945-7170
2DOI: 10.1210/en.2016-1842
3PMID: 28200172
languageeng
publisherWashington, DC: Endocrine Society
subjectAbridged Index Medicus ; Acetates - administration & dosage ; Acetates - therapeutic use ; Adrenoleukodystrophy ; Adrenoleukodystrophy - blood ; Adrenoleukodystrophy - drug therapy ; Adrenoleukodystrophy - genetics ; Adrenoleukodystrophy - metabolism ; Animals ; ATP Binding Cassette Transporter, Sub-Family D ; ATP Binding Cassette Transporter, Sub-Family D, Member 1 ; ATP-Binding Cassette Transporters - deficiency ; ATP-Binding Cassette Transporters - genetics ; ATP-Binding Cassette Transporters - metabolism ; Biological Transport ; Blood ; Brain - metabolism ; Cell Line ; Central nervous system ; Chains ; Complementation ; Demyelination ; Disease ; Editor's Choice ; endocrine system ; endocrine system diseases ; Fatty acids ; Fatty Acids - blood ; Fatty Acids - metabolism ; Fibroblasts ; Fish oils ; Genetic disorders ; Homology ; Humans ; Male ; Metabolism in Endocrine Health ; Metabolism in Endocrine Health and Disease ; Mice ; Mutation ; Organs ; Oxidation ; Peroxisomes ; Peroxisomes - metabolism ; Pharmacology ; Phenols - administration & dosage ; Phenols - therapeutic use ; Receptors, Thyroid Hormone - agonists ; Special Section ; Strategy ; Thyroid ; Thyroid gland ; Thyroid Hormones - administration & dosage ; Thyroid Hormones - metabolism ; Thyroid Hormones - therapeutic use ; Transporter
ispartofEndocrinology (Philadelphia), 2017-05-01, Vol.158 (5), p.1328-1338
rights
0Copyright © 2017 Endocrine Society 2017
1Copyright © 2017 Endocrine Society.
2Copyright © 2017 Endocrine Society
lds50peer_reviewed
oafree_for_read
citedbyFETCH-LOGICAL-1519t-8e0c8951728595e5cd986d5f0d0883ed3365a945dcdaf649b091f510d1889f450
citesFETCH-LOGICAL-1519t-8e0c8951728595e5cd986d5f0d0883ed3365a945dcdaf649b091f510d1889f450
links
openurl$$Topenurl_article
thumbnail$$Usyndetics_thumb_exl
backlink$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28200172$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0Hartley, Meredith D
1Kirkemo, Lisa L
2Banerji, Tapasree
3Scanlan, Thomas S
title
0A Thyroid Hormone–Based Strategy for Correcting the Biochemical Abnormality in X-Linked Adrenoleukodystrophy
1Endocrinology (Philadelphia)
addtitleEndocrinology
descriptionAbstract X-linked adrenoleukodystrophy (X-ALD) is a rare, genetic disorder characterized by adrenal insufficiency and central nervous system (CNS) demyelination. All patients with X-ALD have the biochemical abnormality of elevated blood and tissue levels of very long chain fatty acids (VLCFAs), saturated fatty acids with 24 to 26 carbons. X-ALD results from loss of function mutations in the gene encoding the peroxisomal transporter ABCD1, which is responsible for uptake of VLCFAs into peroxisomes for degradation by oxidation. One proposed therapeutic strategy for genetic complementation of ABCD1 is pharmacologic upregulation of ABCD2, a gene encoding a homologous peroxisomal transporter. Here, we show that thyroid hormone or sobetirome, a clinical-stage selective thyroid hormone receptor agonist, increases cerebral Abcd2 and lowers VLCFAs in blood, peripheral organs, and brains of mice with defective Abcd1. These results support an approach to treating X-ALD that involves a thyromimetic agent that reactivates VLCFA disposal both in the periphery and the CNS. Thyroid hormone and the thyromimetic sobetirome lower CNS levels of very long chain fatty acids in a mouse model of X-linked adrenoleukodystrophy supporting a therapeutic strategy for X-ALD.
subject
0Abridged Index Medicus
1Acetates - administration & dosage
2Acetates - therapeutic use
3Adrenoleukodystrophy
4Adrenoleukodystrophy - blood
5Adrenoleukodystrophy - drug therapy
6Adrenoleukodystrophy - genetics
7Adrenoleukodystrophy - metabolism
8Animals
9ATP Binding Cassette Transporter, Sub-Family D
10ATP Binding Cassette Transporter, Sub-Family D, Member 1
11ATP-Binding Cassette Transporters - deficiency
12ATP-Binding Cassette Transporters - genetics
13ATP-Binding Cassette Transporters - metabolism
14Biological Transport
15Blood
16Brain - metabolism
17Cell Line
18Central nervous system
19Chains
20Complementation
21Demyelination
22Disease
23Editor's Choice
24endocrine system
25endocrine system diseases
26Fatty acids
27Fatty Acids - blood
28Fatty Acids - metabolism
29Fibroblasts
30Fish oils
31Genetic disorders
32Homology
33Humans
34Male
35Metabolism in Endocrine Health
36Metabolism in Endocrine Health and Disease
37Mice
38Mutation
39Organs
40Oxidation
41Peroxisomes
42Peroxisomes - metabolism
43Pharmacology
44Phenols - administration & dosage
45Phenols - therapeutic use
46Receptors, Thyroid Hormone - agonists
47Special Section
48Strategy
49Thyroid
50Thyroid gland
51Thyroid Hormones - administration & dosage
52Thyroid Hormones - metabolism
53Thyroid Hormones - therapeutic use
54Transporter
issn
00013-7227
11945-7170
fulltextfalse
rsrctypearticle
creationdate2017
recordtypearticle
recordideNp1ks1uEzEUhUcIRNPCjjUaiQUsmGJ7_LtBSiMgSJFYUCR2ljO-k3E7sYPHgzQ73qFvyJPgkFDRSl1Zlr97fO7RKYoXGJ1jgtE78OcEYV5hScmjYoYVZZXAAj0uZgjhuhKEiJPidBiu8pVSWj8tTogk-SLIrPDz8rKbYnC2XIa4DR5-_7q5MAPY8muKJsFmKtsQy0WIEZrk_KZMHZQXLjQdbF1j-nK-9nnS9C5NpfPl92rl_HWen9sIPvQwXgc7DSmGXTc9K560ph_g-fE8K759_HC5WFarL58-L-arCjOsUiUBNVKx7FAyxYA1VkluWYsskrIGW9ecmbyobaxpOVVrpHDLMLJYStVShs6K9wfd3bjegm3A52V6vYtua-Kkg3H67ot3nd6En5pRjiRRWWB5EAg78MZFuDNrPSQdrCZcaGYokQKsIKauiZQcK4I5z46JFZjiLPXm6CWGHyMMSW_d0EDfGw9hHDSWXCHOEdmjr-6hV2GMPielseJKUSyFyNTbA9XEMAwR2ltvGOl9JzR4ve-E3nci4y__z-IW_leCDJB7eo1LJrmwj8b1D6m-PgY07h76_28n0R87u83f
startdate20170501
enddate20170501
creator
0Hartley, Meredith D
1Kirkemo, Lisa L
2Banerji, Tapasree
3Scanlan, Thomas S
general
0Endocrine Society
1Oxford University Press
scope
0CGR
1CUY
2CVF
3ECM
4EIF
5NPM
6AAYXX
7CITATION
87QG
97QP
107QR
117T5
127TM
137TO
147U7
158FD
16C1K
17FR3
18H94
19K9.
20P64
217X8
22BOBZL
23CLFQK
245PM
sort
creationdate20170501
titleA Thyroid Hormone–Based Strategy for Correcting the Biochemical Abnormality in X-Linked Adrenoleukodystrophy
authorHartley, Meredith D ; Kirkemo, Lisa L ; Banerji, Tapasree ; Scanlan, Thomas S
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-1519t-8e0c8951728595e5cd986d5f0d0883ed3365a945dcdaf649b091f510d1889f450
rsrctypearticles
prefilterarticles
languageeng
creationdate2017
topic
0Abridged Index Medicus
1Acetates - administration & dosage
2Acetates - therapeutic use
3Adrenoleukodystrophy
4Adrenoleukodystrophy - blood
5Adrenoleukodystrophy - drug therapy
6Adrenoleukodystrophy - genetics
7Adrenoleukodystrophy - metabolism
8Animals
9ATP Binding Cassette Transporter, Sub-Family D
10ATP Binding Cassette Transporter, Sub-Family D, Member 1
11ATP-Binding Cassette Transporters - deficiency
12ATP-Binding Cassette Transporters - genetics
13ATP-Binding Cassette Transporters - metabolism
14Biological Transport
15Blood
16Brain - metabolism
17Cell Line
18Central nervous system
19Chains
20Complementation
21Demyelination
22Disease
23Editor's Choice
24endocrine system
25endocrine system diseases
26Fatty acids
27Fatty Acids - blood
28Fatty Acids - metabolism
29Fibroblasts
30Fish oils
31Genetic disorders
32Homology
33Humans
34Male
35Metabolism in Endocrine Health
36Metabolism in Endocrine Health and Disease
37Mice
38Mutation
39Organs
40Oxidation
41Peroxisomes
42Peroxisomes - metabolism
43Pharmacology
44Phenols - administration & dosage
45Phenols - therapeutic use
46Receptors, Thyroid Hormone - agonists
47Special Section
48Strategy
49Thyroid
50Thyroid gland
51Thyroid Hormones - administration & dosage
52Thyroid Hormones - metabolism
53Thyroid Hormones - therapeutic use
54Transporter
toplevelpeer_reviewed
creatorcontrib
0Hartley, Meredith D
1Kirkemo, Lisa L
2Banerji, Tapasree
3Scanlan, Thomas S
collection
0Medline
1MEDLINE
2MEDLINE (Ovid)
3MEDLINE
4MEDLINE
5PubMed
6CrossRef
7Animal Behavior Abstracts
8Calcium & Calcified Tissue Abstracts
9Chemoreception Abstracts
10Immunology Abstracts
11Nucleic Acids Abstracts
12Oncogenes and Growth Factors Abstracts
13Toxicology Abstracts
14Technology Research Database
15Environmental Sciences and Pollution Management
16Engineering Research Database
17AIDS and Cancer Research Abstracts
18ProQuest Health & Medical Complete (Alumni)
19Biotechnology and BioEngineering Abstracts
20MEDLINE - Academic
21OpenAIRE (Open Access)
22OpenAIRE
23PubMed Central (Full Participant titles)
jtitleEndocrinology (Philadelphia)
delivery
delcategoryRemote Search Resource
fulltextno_fulltext
addata
au
0Hartley, Meredith D
1Kirkemo, Lisa L
2Banerji, Tapasree
3Scanlan, Thomas S
formatjournal
genrearticle
ristypeJOUR
atitleA Thyroid Hormone–Based Strategy for Correcting the Biochemical Abnormality in X-Linked Adrenoleukodystrophy
jtitleEndocrinology (Philadelphia)
addtitleEndocrinology
date2017-05-01
risdate2017
volume158
issue5
spage1328
epage1338
pages1328-1338
issn0013-7227
eissn1945-7170
notesThese authors contributed equally to this study.
abstractAbstract X-linked adrenoleukodystrophy (X-ALD) is a rare, genetic disorder characterized by adrenal insufficiency and central nervous system (CNS) demyelination. All patients with X-ALD have the biochemical abnormality of elevated blood and tissue levels of very long chain fatty acids (VLCFAs), saturated fatty acids with 24 to 26 carbons. X-ALD results from loss of function mutations in the gene encoding the peroxisomal transporter ABCD1, which is responsible for uptake of VLCFAs into peroxisomes for degradation by oxidation. One proposed therapeutic strategy for genetic complementation of ABCD1 is pharmacologic upregulation of ABCD2, a gene encoding a homologous peroxisomal transporter. Here, we show that thyroid hormone or sobetirome, a clinical-stage selective thyroid hormone receptor agonist, increases cerebral Abcd2 and lowers VLCFAs in blood, peripheral organs, and brains of mice with defective Abcd1. These results support an approach to treating X-ALD that involves a thyromimetic agent that reactivates VLCFA disposal both in the periphery and the CNS. Thyroid hormone and the thyromimetic sobetirome lower CNS levels of very long chain fatty acids in a mouse model of X-linked adrenoleukodystrophy supporting a therapeutic strategy for X-ALD.
copWashington, DC
pubEndocrine Society
pmid28200172
doi10.1210/en.2016-1842
oafree_for_read