Abstract：
:This review concerns the development of small molecule therapeutics for the inherited neurodegenerative disease Friedreich ataxia (FRDA). FRDA is caused by transcriptional repression of the nuclear FXN gene, encoding the essential mitochondrial protein frataxin and accompanying loss of frataxin protein. Frataxin insufficiency leads to mitochrondrial dysfunction and progressive neurodegeneration, along with scoliosis, diabetes and cardiomyopathy. Individuals with FRDA generally die in early adulthood from the associated heart disease, the most common cause of death in FRDA. While antioxidants and iron chelators have shown promise in ameliorating the symptoms of the disease, there is no effective therapy for FRDA that addresses the cause of the disease, the loss of frataxin protein. Gene therapy and protein replacement strategies for FRDA are promising approaches; however, current technology is not sufficiently advanced to envisage treatments for FRDA coming from these approaches in the near future. Since the FXN mutation in FRDA, expanded GAA.TTC triplets in an intron, does not alter the amino acid sequence of frataxin protein, gene reactivation would be of therapeutic benefit. Thus, a number of laboratories have focused on small molecule activators of FXN gene expression as potential therapeutics, and this review summarizes the current status of these efforts, as well as the molecular basis for gene silencing in FRDA.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Gottesfeld JMdoi
10.1016/j.pharmthera.2007.06.014subject
Has Abstractpub_date
2007-11-01 00:00:00pages
236-48issue
2eissn
0163-7258issn
1879-016Xpii
S0163-7258(07)00151-9journal_volume
116pub_type
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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pub_type： 杂志文章,评审
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doi：10.1016/j.pharmthera.2014.12.005
更新日期：2015-04-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：1991-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2008-09-01 00:00:00
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doi：10.1016/j.pharmthera.2017.05.007
更新日期：2017-11-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.03.001
更新日期：2012-06-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.05.002
更新日期：2007-07-01 00:00:00
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journal_title：Pharmacology & therapeutics
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更新日期：2011-08-01 00:00:00
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)00047-7
更新日期：1995-01-01 00:00:00
abstract：:Cardiovascular diseases (CVDs) remain the leading cause of death in the developed countries. Taking into account the mounting evidence about the role of cytochrome P450 (CYP) enzymes in cardiovascular physiology, CYP polymorphisms can be considered one of the major determinants of individual susceptibility to CVDs. On...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2010-03-01 00:00:00
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journal_title：Pharmacology & therapeutics
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doi：10.1016/j.pharmthera.2005.06.016
更新日期：2006-01-01 00:00:00
