Wayne State Univ, ?.
Luan Wang. Inst Environmental Hlth Sci, Wayne State Univ, Detroit, MI.
Keywords: Friedreich’s Ataxia (FRDA), Drosophila model for FRDA, UAS-Gal4 system, heart (tinman), neurons (elav), whole body (actin and daG32), reactive oxygen species (ROS) reagent, oxidative stress, autophagy activity.
"This suggests that there is a threshold for frataxin level to maintain the normal function."
Friday, February 3, 2012
Thursday, February 2, 2012
OX1 for Friedreich's Ataxia likely would enter Phase 2 clinical trials early in 2013
NEW YORK, Feb.2, 2012 /PRNewswire/ --Intellect Neurosciences, Inc. (OTCBB:ILNS), a biopharmaceutical company engaged in the discovery and development of disease-modifying therapeutic agents for the treatment of Alzheimer's and other neurological diseases today issued the following Letter to Shareholders from Dr. Daniel Chain, Chairman and CEO.
ViroPharma's CEO, spoke enthusiastically about his company's plans to develop OX1 for Friedreich's Ataxia, indicating OX1 likely would enter Phase 2 clinical trials early in 2013.
ViroPharma's CEO, spoke enthusiastically about his company's plans to develop OX1 for Friedreich's Ataxia, indicating OX1 likely would enter Phase 2 clinical trials early in 2013.
Drugs and mitochondrial diseases: 40 queries and answers
Expert Opinion on Pharmacotherapy 0 0:0, 1-17, Posted online on January 31, 2012. (doi:10.1517/14656566.2012.657177)
Michelangelo Mancuso †1 MD PhD, Daniele Orsucci 1, Massimiliano Filosto 2, Costanza Simoncini 1 & Gabriele Siciliano 1
1 University of Pisa, Neurological Clinic, Department of Neuroscience,
Via Roma 67, 56126 Pisa, Italy
2 University of Brescia, Italy
Keywords
carnitine, coenzyme Q10, creatine, mitochondria, mitochondrial diseases, mtDNA, riboflavin, Mitochondrial disorders, oxidative phosphorylation, respiratory chain cofactors, antioxidants, lactic acidosis, basic and clinical literature.
Michelangelo Mancuso †1 MD PhD, Daniele Orsucci 1, Massimiliano Filosto 2, Costanza Simoncini 1 & Gabriele Siciliano 1
1 University of Pisa, Neurological Clinic, Department of Neuroscience,
Via Roma 67, 56126 Pisa, Italy
2 University of Brescia, Italy
Keywords
carnitine, coenzyme Q10, creatine, mitochondria, mitochondrial diseases, mtDNA, riboflavin, Mitochondrial disorders, oxidative phosphorylation, respiratory chain cofactors, antioxidants, lactic acidosis, basic and clinical literature.
Nrf2 and oxidative stress protection
Role of nuclear factor (erythroid-derived 2)-like 2 in metabolic homeostasis
and insulin action: A novel opportunity for diabetes treatment?
World J Diabetes. 2012 January 15; 3(1): 19-28.
Published online 2012 January 15. doi: 10.4239/wjd.v3.i1.19.
FULL TEXT PDF
Zhi-Wen Yu, Dan Li, Wen-Hua Ling and Tian-Ru Jin.
Zhi-Wen Yu, Dan Li, Wen-Hua Ling, Tian-Ru Jin, Guandong Provincial Key
Laboratory of Food, Nutrition and Health, Department of Nutrition, Public
Health Institute, Sun Yat-Sen University, Guangzhou 510080, Guangdong
Province, China
Tian-Ru Jin, Division of Cell and Molecular Biology, Toronto General
Research Institute, University Health Network, Toronto M5G 1L7, Canada
"As the major cellular defense machinery against oxidative stress, the Nrf2
system has drawn extensive attention. However, its functional alteration in
metabolic diseases has been realized recently and needs to be explored
further. Impaired Nrf2 function is evident in several pathological
conditions, such as aging, neurodegeneration diseases and insulin
resistance, that are mechanistically linked to oxidative stress, while Nrf2
activation reverses the functional abnormality of these diseases"
Nrf2, a Guardian of Healthspan and Gatekeeper of Species Longevity
Integr. Comp. Biol. (2010) doi: 10.1093/icb/icq034
Kaitlyn N. Lewis*†‡, James Mele†‡, John D. Hayes§ and Rochelle Buffenstein1,*†‡
*Department of Cellular and Structural Biology, University of Texas
Health Science Center at San Antonio, 15355 Lambda Drive, STCBM 2.2, San
Antonio TX 78245, USA; †Department of Physiology, University of Texas Health
Science Center at San Antonio, 15355 Lambda Drive, STCBM 2.2, San Antonio TX
78245, USA; ‡Sam and Anne Barshop Institute for Aging and Longevity Studies,
University of Texas Health Science Center at San Antonio, 15355 Lambda
Drive, STCBM 2.2, San Antonio TX 78245, USA; §Biomedical Research Centre,
University of Dundee, Dundee DD1 9SY, Scotland, UK
"The Nrf2-signaling pathway mediates multiple avenues of cytoprotection by activating the transcription of more than 200 genes that are crucial in the metabolism of drugs and toxins, protection against oxidative stress and inflammation, as well as playing an integral role in stability of proteins and in the removal of damaged proteins via proteasomal degradation or autophagy. Nrf2 interacts with other important cell regulators such as tumor suppressor protein 53 (p53) and nuclear factor-kappa beta (NF-κB) and through their combined interactions is the guardian of healthspan, protecting against many age-related diseases including cancer and neurodegeneration."
FULL TEXT PDF
Genetic activation of Nrf2 signaling is sufficient to ameliorate
neurodegenerative phenotypes in a Drosophila model of Parkinson’s disease.
Dis Model Mech. 2011 September; 4(5): 701–707.
Published online 2011 June 30. doi: 10.1242/dmm.007575
Maria Cecilia Barone,1 Gerasimos P. Sykiotis,2 and Dirk Bohmann1*
1Department of Biomedical Genetics, University of Rochester Medical Center,
Rochester, NY 14642, USA
2Division of Endocrinology, Department of Internal Medicine and Department
of Pharmacology, University of Patras Medical School, Patras 26500, Greece
"The transcription factor Nrf2, a conserved global regulator of cellular antioxidant responses, has been implicated in neuroprotection against PD pathology."
"Our data validate the sustained upregulation of the Nrf2 pathway as a neuroprotective strategy against PD."
FULL TEXT PDF
and insulin action: A novel opportunity for diabetes treatment?
World J Diabetes. 2012 January 15; 3(1): 19-28.
Published online 2012 January 15. doi: 10.4239/wjd.v3.i1.19.
FULL TEXT PDF
Zhi-Wen Yu, Dan Li, Wen-Hua Ling and Tian-Ru Jin.
Zhi-Wen Yu, Dan Li, Wen-Hua Ling, Tian-Ru Jin, Guandong Provincial Key
Laboratory of Food, Nutrition and Health, Department of Nutrition, Public
Health Institute, Sun Yat-Sen University, Guangzhou 510080, Guangdong
Province, China
Tian-Ru Jin, Division of Cell and Molecular Biology, Toronto General
Research Institute, University Health Network, Toronto M5G 1L7, Canada
"As the major cellular defense machinery against oxidative stress, the Nrf2
system has drawn extensive attention. However, its functional alteration in
metabolic diseases has been realized recently and needs to be explored
further. Impaired Nrf2 function is evident in several pathological
conditions, such as aging, neurodegeneration diseases and insulin
resistance, that are mechanistically linked to oxidative stress, while Nrf2
activation reverses the functional abnormality of these diseases"
Nrf2, a Guardian of Healthspan and Gatekeeper of Species Longevity
Integr. Comp. Biol. (2010) doi: 10.1093/icb/icq034
Kaitlyn N. Lewis*†‡, James Mele†‡, John D. Hayes§ and Rochelle Buffenstein1,*†‡
*Department of Cellular and Structural Biology, University of Texas
Health Science Center at San Antonio, 15355 Lambda Drive, STCBM 2.2, San
Antonio TX 78245, USA; †Department of Physiology, University of Texas Health
Science Center at San Antonio, 15355 Lambda Drive, STCBM 2.2, San Antonio TX
78245, USA; ‡Sam and Anne Barshop Institute for Aging and Longevity Studies,
University of Texas Health Science Center at San Antonio, 15355 Lambda
Drive, STCBM 2.2, San Antonio TX 78245, USA; §Biomedical Research Centre,
University of Dundee, Dundee DD1 9SY, Scotland, UK
"The Nrf2-signaling pathway mediates multiple avenues of cytoprotection by activating the transcription of more than 200 genes that are crucial in the metabolism of drugs and toxins, protection against oxidative stress and inflammation, as well as playing an integral role in stability of proteins and in the removal of damaged proteins via proteasomal degradation or autophagy. Nrf2 interacts with other important cell regulators such as tumor suppressor protein 53 (p53) and nuclear factor-kappa beta (NF-κB) and through their combined interactions is the guardian of healthspan, protecting against many age-related diseases including cancer and neurodegeneration."
FULL TEXT PDF
Genetic activation of Nrf2 signaling is sufficient to ameliorate
neurodegenerative phenotypes in a Drosophila model of Parkinson’s disease.
Dis Model Mech. 2011 September; 4(5): 701–707.
Published online 2011 June 30. doi: 10.1242/dmm.007575
Maria Cecilia Barone,1 Gerasimos P. Sykiotis,2 and Dirk Bohmann1*
1Department of Biomedical Genetics, University of Rochester Medical Center,
Rochester, NY 14642, USA
2Division of Endocrinology, Department of Internal Medicine and Department
of Pharmacology, University of Patras Medical School, Patras 26500, Greece
"The transcription factor Nrf2, a conserved global regulator of cellular antioxidant responses, has been implicated in neuroprotection against PD pathology."
"Our data validate the sustained upregulation of the Nrf2 pathway as a neuroprotective strategy against PD."
FULL TEXT PDF
Wednesday, February 1, 2012
A Revelation by the Yeast Model System
Degree Essays, ?.
Keywords: Friedreich Ataxia (FA), cardiomyopathy, diabetes mellitus, scoliosis, GAA trinucleotide repeats, iron, chelate iron, idebenone, Heat-shock protein (HSP) induction, manganese.
Keywords: Friedreich Ataxia (FA), cardiomyopathy, diabetes mellitus, scoliosis, GAA trinucleotide repeats, iron, chelate iron, idebenone, Heat-shock protein (HSP) induction, manganese.
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.
Subscribe to:
Posts (Atom)
