Modelling Friedreich's Ataxia Using Human Induced Pluripotent Stem Cells

The Scripps Research Institute Graduate Program. Thesis for the degree of Doctor of Philosophy in the subject of Biology.La Jolla,California March 2011.

Sherman Ku

Keywords: Friedreich’s ataxia (FRDA), GAA•TTC triplet repeat expansion, heterochromatin-mediated compaction, frataxin gene, induced pluripotent stemcells (iPSCs), fibroblasts, MSH2.

MOLECULAR DETAILS OF THE PROTEINS INVOLVED MITOCHONDRIAL IRON-SULFUR CLUSTER ASSEMBLY

Wayne State University Theses. Paper 148. (2011)

YOGAPRIYA MURUGESAN

Keywords: Friedrich's ataxia, frataxin, Fe-S cluster assembly, reactive oxygen species, cysteine desulfurase Nfs1, scaffold protein Isu, metal iron.

The Role of Iron in Retinal Diseases

Humana Press. Studies on Retinal and Choroidal Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice, 2012, 259-275,Isbn: 978-1-61779-606-7, Doi: 10.1007/978-1-61779-606-7_12

Sonia Mehta and Joshua L. Dunaief.

Keywords: Iron, free radical generator, retina, macula, oxidative damage, aceruloplasminemia, Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration, iron overload.

Biochemical Characterization of Iron-Sulfur Cluster Assembly in the Scaffold IscU of Escherichia coli.

Biochemistry (Mosc). 2012 Feb;77(2):135-42.

Wu G, Li L.
College of Life Science, Zhejiang University, Hangzhou, 310058, China.

Keywords: Iron-sulfur cluster, IscU, iron, cysteine, environmental pH, IscS, first order reaction, mixed order reaction, zero order reaction, apo-IscU.

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Effector role reversal during evolution: the case of frataxin in Fe-S cluster biosynthesis

Biochemistry, Just Accepted Manuscript, DOI: 10.1021/bi201628j, Publication Date (Web): February 21, 2012

Jennifer Bridwell-Rabb, Clara Iannuzzi, Annalisa Pastore, and David P. Barondeau

Keywords: frataxin (FXN), Friedreich’s ataxia, NFS1-ISD11-ISCU2-FXN (SDUF) core Fe-S assembly complex, cysteine desulfurase, Fe-S cluster biosynthesis.

Cognition in Friedreich Ataxia.

Cerebellum. 2012 Feb 16.

Nieto A, Correia R, de Nóbrega E, Montón F, Hess S, Barroso J.
School of Psychology, University of La Laguna, 38205, La Laguna, Tenerife, Spain,

Keywords: Friedreich ataxia (FRDA), cognitive status, motor problems, processing speed, attention, working memory, executive functions, verbal and visual memory, visuoperceptive and visuospatial skills, visuoconstructive functions, language, depression inventory, executive problems, parieto-temporal dysfunction, mild anomalies in cerebral hemispheres, cerebro-cerebellar circuits..

Histone Deacetylase Complexes Promote Trinucleotide Repeat Expansions

PLoS Biol 10(2): e1001257. doi:10.1371/journal.pbio.1001257

Kim Debacker#, Aisling Frizzell#, Olive Gleeson, Lucy Kirkham-McCarthy, Tony Mertz, Robert S. Lahue*
Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland

OPEN ACCESS

Currently some researchers and pharmaceutical labs are testing HDACi for relief of the transcription-related consequences of expansions in triplet expansion diseases, they may also have the beneficial side effect of reducing the risk of further somatic expansion.

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Mitochondrial disorders: a review of anesthetic considerations

Middle East Journal of Anesthesiology, (M.E.J. ANESTH 21 (2), 2011), 02/20/2012

HERODOTOS ELLINAS* AND ELIZABETH A.M. FROST**,
* Assistant Professor, Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI.
** Professor of Anesthesia, Mount Sinai Medical Center, New York, NY.

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Discussions about treatment restrictions in chronic neurologic diseases: A structured review

Neurology February 21, 2012 78:590-597

Antje A. Seeber, Albert Hijdra, Marinus Vermeulen, and Dick L. Willems
Department of Neurology (A.A.S., A.H., and M.V.) and Department of Medical Ethics, Division of Public Health & Epidemiology (A.A.S. and D.L.W.), Academic Medical Center, University of Amsterdam, the Netherlands.

Anticipation of such situations may be beneficial for patients and their families.

Uses of the postural stability test for differential diagnosis of hereditary ataxias.

J Neurol Sci. 2012 Feb 13. http://dx.doi.org/10.1016/j.jns.2012.01.022.

J. Schwabova a, F. Zahalka c, V. Komarek b, T. Maly c, P. Hrasky c, T. Gryc c, O. Cakrt d, A. Zumrova b

a Department of Neurology, Charles University in Prague, 2nd Faculty of Medicine and the Motol University Hospital, V Úvalu 84, Prague 5, 150 06, Czech republic
b Department of Paediatric Neurology, Charles University in Prague, 2nd Faculty of Medicine and the Motol University Hospital, V Úvalu 84, Prague 5, 150 06, Czech republic
c Research Sport Center, Charles University in Prague, Faculty of Physical Education and Sport, Jose Martího 31, Prague 6, 162 52, Czech republic
d Department of Rehabilitation and Sport Medicine, Charles University in Prague, 2nd Faculty of Medicine and the Motol University Hospital, V Úvalu 84, Prague 5, 150 06, Czech republic

Keywords: Friedreich's ataxia (FRDA), spinocerebellar ataxia type 2 (SCA 2), posturographic examination, differential diagnosis.

The Autosomal Recessive Cerebellar Ataxias

N Engl J Med 2012; 366:636-646, February 16, 2012

Mathieu Anheim, M.D., Ph.D., Christine Tranchant, M.D., and Michel Koenig, M.D., Ph.D.

Review Article

Substantia nigra hypoechogenicity in Friedreich ataxia.

Mov Disord 2012 Feb; 27(2):332-3.DOI: 10.1002/mds.23989

Stockner H, Sojer M, Hering S, Nachbauer W, Seppi K, Schmidauer C, Poewe W, Boesch SM
Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

No abstract is available for this article.

Histone deacetylase inhibition activates transcription factor Nrf2 and protects against cerebral ischemic damage.

Free Radic Biol Med. Volume 52, Issue 5, 1 March 2012, Pages 928–936, http://dx.doi.org/10.1016/j.freeradbiomed.2011.12.006

Wang B, Zhu X, Kim Y, Li J, Huang S, Saleem S, Li RC, Xu Y, Dore S, Cao W.

Nanjing University Medical School, Jiangsu Key Lab of Molecular Medicine,
Nanjing, People's Republic of China; Department of Anesthesiology and Critical
Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205,
USA.

Keywords: histone deacetylase (HDAC), neuroprotection, multiple mechanisms, modulation of transcription, Nrf2, stroke, antioxidant-responsive genes, activation of Nrf2.

Cognitive function in Friedreich's ataxia patients in Ireland

J Neurol Neurosurg Psychiatry 2012;83:e1 doi:10.1136/jnnp-2011-301993.43

C Albertyn, N Austin, R P Murphy
Adelaide and Meath Hospital, Dublin, Ireland

Keywords: Friedreich's ataxia (FRDA), cognitive function, genetically confirmed FRDA patients, age of onset, duration of symptoms, Friedreich's ataxia rating scale (FARS) score, neuropsychological test battery assessed immediate and delayed verbal memory, visuospatial perception, confrontational naming, non-verbal memory, attention and concentration, premorbid intellect, executive function, cognitive speed.

Determination of Idebenone in Plasma by HPLC with Post -Column Fluorescence Derivatization using 2-Cyanoacetamide

Chem Pharm Bull, Regular Article, Analytical Chemistry

Yukio NOHARA a, Junko SUZUKI b, Yoji YAMAZAKI a, Hiroaki KUBO a.
a Faculty of Pharmacy, Iwaki Meisei University, Iwaki, Fukushima 970-8551, Japan
b School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan

Keywords: Idebenone, Friedreich’s ataxia, 2-cyanoacetamide, fluorescence, HPLC with post-column fluorescence derivatization, human blood plasma, finger prick.

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A Drosophila Model of Friedreich's Ataxia and Autophagic Heart Disease.

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."

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.

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.

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.

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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."

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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."


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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.