Degree Essays, ?.
Keywords: Friedreich Ataxia (FA), cardiomyopathy, diabetes mellitus, scoliosis, GAA trinucleotide repeats, iron, chelate iron, idebenone, Heat-shock protein (HSP) induction, manganese.
Wednesday, February 1, 2012
Tuesday, January 31, 2012
Neurological diseases remain neglected and ignored
The Lancet, Volume 379, Issue 9813, Page 287, 28 January 2012, doi:10.1016/S0140-6736(12)60123-8
Editorial
"A clinical champion for neurology who will present a national strategy with clear targets, an inbuilt monitoring and data collection system, and priorities for research is urgently needed and long overdue."
Editorial
"A clinical champion for neurology who will present a national strategy with clear targets, an inbuilt monitoring and data collection system, and priorities for research is urgently needed and long overdue."
Monday, January 30, 2012
Is Friedreich ataxia an epigenetic disorder?
Clinical Epigenetics 2012, 4:2 doi:10.1186/1868-7083-4-2
Published: 30 January 2012 (OPEN ACCESS)
Daman Kumari and Karen Usdin
Abstract (provisional)
Friedreich ataxia (FRDA) is a debilitating and frequently fatal neurological disorder that is recessively inherited. It belongs to the group of genetic disorders known as the Repeat Expansion Diseases in which pathology arises from the deleterious consequences of the inheritance of a tandem repeat array whose repeat number exceeds a critical threshold. In the case of FRDA, the repeat unit is the triplet GAA*TTC and the tandem array is located in the first intron of the FXN gene. Pathology arises because expanded alleles make lower than normal levels of mature FXN mRNA and thus reduced levels of frataxin, the FXN gene product. The repeats form a variety of unusual DNA structures including triplexes. They also form persistent RNA:DNA hybrids in vitro and in bacteria and affect splicing in model systems. More recently the repeats in the FXN gene have also been shown to be enriched for epigenetic marks that are characteristic of transcriptionally repressed regions of the genome. However, exactly how repeats in an intron cause the FXN mRNA deficit in FRDA has been the subject of much debate. Identifying the mechanism or mechanisms responsible for the FXN mRNA deficit in FRDA is important for the development of treatments for this currently incurable disorder. This review discusses evidence for and against possible models for the repeat-mediated mRNA deficit.
Full text pdf
Published: 30 January 2012 (OPEN ACCESS)
Daman Kumari and Karen Usdin
Abstract (provisional)
Friedreich ataxia (FRDA) is a debilitating and frequently fatal neurological disorder that is recessively inherited. It belongs to the group of genetic disorders known as the Repeat Expansion Diseases in which pathology arises from the deleterious consequences of the inheritance of a tandem repeat array whose repeat number exceeds a critical threshold. In the case of FRDA, the repeat unit is the triplet GAA*TTC and the tandem array is located in the first intron of the FXN gene. Pathology arises because expanded alleles make lower than normal levels of mature FXN mRNA and thus reduced levels of frataxin, the FXN gene product. The repeats form a variety of unusual DNA structures including triplexes. They also form persistent RNA:DNA hybrids in vitro and in bacteria and affect splicing in model systems. More recently the repeats in the FXN gene have also been shown to be enriched for epigenetic marks that are characteristic of transcriptionally repressed regions of the genome. However, exactly how repeats in an intron cause the FXN mRNA deficit in FRDA has been the subject of much debate. Identifying the mechanism or mechanisms responsible for the FXN mRNA deficit in FRDA is important for the development of treatments for this currently incurable disorder. This review discusses evidence for and against possible models for the repeat-mediated mRNA deficit.
Full text pdf
Sunday, January 29, 2012
DNA helicase and helicase–nuclease enzymes with a conserved iron–sulfur cluster
Nucl. Acids Res. (2012) doi: 10.1093/nar/gks039 First published online: January 28, 2012 (This article is Open Access)
Yuliang Wu 1 and Robert M. Brosh Jr 2.
1 Department of Biochemistry, University of Saskatchewan, Health Sciences Building, Saskatoon, Saskatchewan, S7N 5E5, Canada
2 Laboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, Baltimore, MD 21224, USA
A defect in the synthesis of Fe–S clusters is responsible for mitochondrial dysfunction, leading to nuclear genomic instability (109). Defects in Fe–S assembly due to a deficiency in the iron storage/transport protein frataxin also lead to genomic instability and defective BER (110), suggesting that the conserved Fe–S cluster in Dna2 and other DNA repair/replication proteins may be crippled due to the frataxin deficiency; however, this remains to be shown. Further studies are required to ascertain the importance of the Fe–S staple domain in Dna2 for its nuclear and mitochondrial functions, and the influence of iron homeostasis in this respect.
Full text pdf
Yuliang Wu 1 and Robert M. Brosh Jr 2.
1 Department of Biochemistry, University of Saskatchewan, Health Sciences Building, Saskatoon, Saskatchewan, S7N 5E5, Canada
2 Laboratory of Molecular Gerontology, National Institute on Aging, NIH, NIH Biomedical Research Center, Baltimore, MD 21224, USA
A defect in the synthesis of Fe–S clusters is responsible for mitochondrial dysfunction, leading to nuclear genomic instability (109). Defects in Fe–S assembly due to a deficiency in the iron storage/transport protein frataxin also lead to genomic instability and defective BER (110), suggesting that the conserved Fe–S cluster in Dna2 and other DNA repair/replication proteins may be crippled due to the frataxin deficiency; however, this remains to be shown. Further studies are required to ascertain the importance of the Fe–S staple domain in Dna2 for its nuclear and mitochondrial functions, and the influence of iron homeostasis in this respect.
Full text pdf
Friday, January 27, 2012
Mutations in rare ataxia genes are uncommon causes of sporadic cerebellar ataxia
Movement Disorders, Article first published online: 27 JAN 2012 | DOI: 10.1002/mds.24064
Brent L. Fogel, Ji Yong Lee, Jessica Lane, Amanda Wahnich, Sandy Chan, Alden Huang, Greg E. Osborn, Eric Klein, Catherine Mamah, Susan Perlman, Daniel H. Geschwind and Giovanni Coppola
Keywords: cerebellar ataxia, copy number variation, dominant genetic conditions, recessive genetic conditions, spinocerebellar ataxia, adult-onset sporadic ataxia, SCA1, SCA2, SCA3, SCA6, SCA7, Friedreich ataxia.
Brent L. Fogel, Ji Yong Lee, Jessica Lane, Amanda Wahnich, Sandy Chan, Alden Huang, Greg E. Osborn, Eric Klein, Catherine Mamah, Susan Perlman, Daniel H. Geschwind and Giovanni Coppola
Keywords: cerebellar ataxia, copy number variation, dominant genetic conditions, recessive genetic conditions, spinocerebellar ataxia, adult-onset sporadic ataxia, SCA1, SCA2, SCA3, SCA6, SCA7, Friedreich ataxia.
Thursday, January 26, 2012
Iron dysregulation in movement disorders.
Neurobiol Dis. 2012 Jan 12. [Epub ahead of print], http://dx.doi.org/10.1016/j.nbd.2011.12.054,
Petr Dusek a, c, Joseph Jankovic a, Weidong Le b
a Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
b Parkinson's Disease Research Laboratory, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
c Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic
Keywords: Iron, neurodegeneration with brain iron accumulation (NBIA), aceruloplasminemia, neuroferritinopathy, Friedreich's ataxia, Parkinson's disease, Huntington's disease, multiple system atrophy, progressive supranuclear palsy.
Petr Dusek a, c, Joseph Jankovic a, Weidong Le b
a Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
b Parkinson's Disease Research Laboratory, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
c Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic
Keywords: Iron, neurodegeneration with brain iron accumulation (NBIA), aceruloplasminemia, neuroferritinopathy, Friedreich's ataxia, Parkinson's disease, Huntington's disease, multiple system atrophy, progressive supranuclear palsy.
A 'Disruptive Science' Ready For Commercial Development - Gene Therapy
Mary Ann Liebert, Inc./Genetic Engineering News. (2012, January 26). "A 'Disruptive Science' Ready For Commercial Development - Gene Therapy." Medical News Today.
"The time for commercial development of gene therapy has come. Patients with diseases treatable and curable with gene therapy deserve access to the technology, which has demonstrated both its effectiveness and feasibility"
"The time for commercial development of gene therapy has come. Patients with diseases treatable and curable with gene therapy deserve access to the technology, which has demonstrated both its effectiveness and feasibility"
Monday, January 23, 2012
The promise of induced pluripotent stem cells in research and therapy
Nature 481, 295–305 (19 January 2012), doi:10.1038/nature10761
Daisy A. Robinton & George Q. Daley
Keywords: stem-cell biology, reprogramming technology, pluripotency, somatic cells, personalized regenerative cell therapies.
Supplementary Table (128K)
Daisy A. Robinton & George Q. Daley
Keywords: stem-cell biology, reprogramming technology, pluripotency, somatic cells, personalized regenerative cell therapies.
Supplementary Table (128K)
The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model
Neurobiology of Disease, Available online 20 January 2012, http://dx.doi.org/10.1016/j.nbd.2012.01.002
Vahid Ezzatizadeh a,Ricardo Mouro Pinto b, Chiranjeevi Sandi a, Madhavi Sandi a, Sahar Al-Mahdawi a, Hein te Riele c, Mark A. Pook a.
a Division of Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, UB8 3PH, UK
b Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
c Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Keywords: Friedreich ataxia (FRDA), GAA repeat expansion mutation, FXN gene, mismatch repair (MMR) proteins, TNR instability, Msh2, Msh3, Msh6, Pms2,
Vahid Ezzatizadeh a,Ricardo Mouro Pinto b, Chiranjeevi Sandi a, Madhavi Sandi a, Sahar Al-Mahdawi a, Hein te Riele c, Mark A. Pook a.
a Division of Biosciences, School of Health Sciences and Social Care, Brunel University, Uxbridge, UB8 3PH, UK
b Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
c Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Keywords: Friedreich ataxia (FRDA), GAA repeat expansion mutation, FXN gene, mismatch repair (MMR) proteins, TNR instability, Msh2, Msh3, Msh6, Pms2,
Saturday, January 21, 2012
Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells
Biochemical and Biophysical Research Communications, Available online 16 January 2012, In Press, Accepted Manuscript. http://dx.doi.org/10.1016/j.bbrc.2012.01.022
Sophie Lefevre a, b, 1, Dominika Sliwa a, 1, Pierre Rustin c, d, Jean-Michel Camadro a, Renata Santos a.
a Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Université Paris-Diderot, Sorbonne Paris Cité, 15 rue Hélène Brion, 75205 Paris cedex 13, France
b ED515 UPMC, 4 place Jussieu 75005 Paris, France
c Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris, France
d Université Paris-Diderot, Faculté de Médecine Denis Diderot, IFR02, Paris, France
Keywords: Friedreich ataxia (FA), mitochondrial frataxin, iron-sulfur cluster assembly, fragmented mitochondria, oxidative stress, mitochondrial dynamics.
Sophie Lefevre a, b, 1, Dominika Sliwa a, 1, Pierre Rustin c, d, Jean-Michel Camadro a, Renata Santos a.
a Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Université Paris-Diderot, Sorbonne Paris Cité, 15 rue Hélène Brion, 75205 Paris cedex 13, France
b ED515 UPMC, 4 place Jussieu 75005 Paris, France
c Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris, France
d Université Paris-Diderot, Faculté de Médecine Denis Diderot, IFR02, Paris, France
Keywords: Friedreich ataxia (FA), mitochondrial frataxin, iron-sulfur cluster assembly, fragmented mitochondria, oxidative stress, mitochondrial dynamics.
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