Neuronal inactivation of PPAR{gamma} Coactivator 1{alpha}(PGC-1{alpha}) protects mice from diet-induced obesity and leads to degenerative lesions.

J Biol Chem. 2010 Oct 13. [Epub ahead of print]

Ma D, Li S, Lucas EK, Cowell RM, Lin JD.
Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan;


These studies have demonstrated a physiological role for neuronal PGC-1α in the control of energy balance and strongly suggest that neuronal PGC-1α exerts profound effects on the neural circuitry that governs systemic energy balance.

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Remark: Interesting conclusions about the action of PGC1-alpha in the neurons, I would like to emphasize that the action of PGC1-a is greatly diminished in the FA.

Structural; Mechanistic and Coordination Chemistry of Relevance to the Biosynthesis of Iron-Sulfur and Related Iron Cofactors

Coordination Chemistry Reviews, doi:10.1016/j.ccr.2010.10.016

Structural; Mechanistic and Coordination Chemistry of Relevance to the Biosynthesis of Iron-Sulfur and Related Iron Cofactors

Wenbin Qi (a) and J.A. Cowan (a,b)

a Ohio State Biochemistry Program, The Ohio State University
b Department of Chemistry, The Ohio State University

Available online 28 October 2010.

Patent application title: FORMULATIONS OF TOCOTRIENOL QUINONES FOR THE TREATMENT OF OPHTHALMIC DISEASES

Inventors: William D. Shrader Viktoria Kheifets Guy M. MILLER

Publication date: 10/28/2010

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14. The method according to claim 6, wherein the ocular symptoms are associated with inherited mitochondrial diseases; Chronic Progressive External Opthalmoplegia (CPEO); Spinocerebellar ataxia (SCA), also called Machado-Joseph disease; Leigh's Syndrome; Friedreich's ataxia (FRDA); Mitochondrial Myopathy, ....

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Research offers clues to mechanisms behind childhood-onset disorder, Friedreich's ataxia

Wayne State University, Public Relations, October 28, 2010.

Wayne State University researcher reviews link between frataxin and iron-sulfur clusters

DETROIT - Friedreich's ataxia is a childhood-onset disorder that causes progressive sensory and muscle loss. The molecular mechanisms and processes behind the incurable disorder are still in question, but a Wayne State University researcher is getting closer to the answer.

Timothy L. Stemmler, Ph.D., associate professor of biochemistry and molecular biology in WSU's School of Medicine, has studied the causality of Friedriech's ataxia......
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Exploration of transitional life events in individuals with Friedreich ataxia: Implications for genetic counseling

Behavioral and Brain Functions 2010, 6:65doi:10.1186/1744-9081-6-65
Published: 27 October 2010

V Brook White1*, Jennifer R Leib 2, Jennifer M Farmer3, Barbara B Biesecker4
1Clinical Genetics, Carolinas Medical Center, PO Box 32861, Charlotte, NC 28232-
2861, USA
2HealthFutures, Washington, DC, USA
3Friedreich’s Ataxia Research Alliance, Exton, PA, USA
4National Human Genome Research Institute, National Institutes of Health,
Bethesda, MD, USA

OPEN ACCESS

Background

Human development is a process of change, adaptation and growth. Throughout this process, transitional events mark important points in time when one's life course is significantly altered. This study captures transitional life events brought about or altered by Friedreich ataxia, a progressive chronic illness leading to disability, and the impact of these events on an affected individual's life course.
Methods

Forty-two adults with Friedreich ataxia (18-65y) were interviewed regarding their perceptions of transitional life events. Data from the interviews were coded and analyzed thematically using an iterative process.
Results

Identified transitions were either a direct outcome of Friedreich ataxia, or a developmental event altered by having the condition. Specifically, an awareness of symptoms, fear of falling and changes in mobility status were the most salient themes from the experience of living with Friedreich ataxia. Developmental events primarily influenced by the condition were one's relationships and life's work.
Conclusions

Friedreich ataxia increased the complexity and magnitude of transitional events for study participants. Transitional events commonly represented significant loss and presented challenges to self-esteem and identity. Findings from this study help alert professionals of potentially challenging times in patients' lives, which are influenced by chronic illness or disability. Implications for developmental counseling approaches are suggested for genetic counseling.

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Research on epigenetic regulation of the CNS

Research on epigenetic regulation of the CNS is a field that is currently being studied for its implications in neuronal regulation. The following papers, although are not about FA, are interesting because they show how these advances can be very important to find a cure for the disease.


Focus on epigenetics
Nature Neuroscience 13, 1299 (2010), Published online: 26 October 2010 | doi:10.1038/nn1110-1299

Epigenetic regulation of the neural transcriptome: the meaning of the marks

Nature Neuroscience 13, 1313 - 1318 (2010), Published online: 26 October 2010 | doi:10.1038/nn1110-1313

Dynamic epigenetic regulation in neurons: enzymes, stimuli and signaling pathways

Nature Neuroscience 13, 1330 - 1337 (2010), Published online: 26 October 2010 | doi:10.1038/nn.2671

Epigenetic choreographers of neurogenesis in the adult mammalian brain
Nature Neuroscience 13, 1338 - 1344 (2010)
Published online: 26 October 2010 | doi:10.1038/nn.2672

The Nrf2 System as a Potential Target for the Development of Indirect Antioxidants

Molecules. 2010 Oct 20;15(10):7266-91.

Kyeong-Ah Jung and Mi-Kyoung Kwak * email
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongsangbuk-do 712-749, Korea

OPEN ACCESS

Abstract:
Oxidative stress causes damage to multiple cellular components such as DNA, proteins, and lipids, and is implicated in various human diseases including cancer, neurodegeneration, inflammatory diseases, and aging. In response to oxidative attack, cells have developed an antioxidant defense system to maintain cellular redox homeostasis and to protect cells from damage. The thiol-containing small molecules (e.g. glutathione), reactive oxygen species-inactivating enzymes (e.g. glutathione peroxidase), and phase 2 detoxifying enzymes (e.g. NAD(P)H: quinine oxidoreductase 1 and glutathione-S-transferases) are members of this antioxidant system. NF-E2-related factor 2 (Nrf2) is a CNC-bZIP transcription factor which regulates the basal and inducible expression of a wide array of antioxidant genes. Following dissociation from the cytosolic protein Keap1, a scaffolding protein which binds Nrf2 and Cul3 ubiquitin ligase for proteasome degradation, Nrf2 rapidly accumulates in the nucleus and transactivates the antioxidant response element in the promoter region of many antioxidant genes. The critical role of Nrf2 has been demonstrated by various animal studies showing that mice with a targeted disruption of the nrf2 gene are prone to develop lesions in response to environmental toxicants/carcinogens, drugs, and inflammatory insults. In this review, we discuss the role of the Nrf2 system, with particular focus on Nrf2-controlled target genes and the potential pleiotropic effects of Nrf2 activation of indirect antioxidants.

Keywords: indirect antioxidants; oxidative stress; Nrf2; Keap1

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Slowing of axonal regeneration is correlated with increased axonal viscosity during aging

BMC Neuroscience 2010, 11:140doi:10.1186/1471-2202-11-140, Published: 25 October 2010

Phillip L Lamoureux, Matthew R O'Toole, Steven R Heidemann and Kyle E Miller

OPEN ACCESS

Conclusions
Taken together, our results suggest decreasing axonal stiffness may be part of an effective strategy to accelerate the regeneration of axons in the adult peripheral nervous system.

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Expression, Purification, and Characterization of an Iron Chaperon Protein CyaY from Acidithiobacillus ferrooxidans

Current Microbiology,DOI: 10.1007/s00284-010-9775-2

Chenbing Ai, Hongyu Mo, Qian Chen, Yuandong Liu, Lin Tang, Juan Du and Jia Zeng

Keywords: CyaY, bacterial homolog of frataxin, iron–sulfur clusters, Acidithiobacillus ferrooxidans, Escherichia coli, affinity chromatography, ferric iron, iron donor, scaffold protein IscU, IscS, l-cysteine.

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Genetic Engineering of Mesenchymal Stem Cells and Its Application in Human Disease Therapy

Conrad P. Hodgkinson, José A. Gomez, Maria Mirotsou, Victor J. Dzau. Human Gene Therapy. -Not available-, ahead of print. doi:10.1089/hum.2010.165.

Keywords: stem cells, tissue regeneration, bone marrow, therapeutic potential, cardiovascular injury, kidney failure, cancer, neurological and bone disorders. low survival, engraftment, inefficiencies in differentiating into fully functional tissues, genetic engineering, mesenchymal stem cells, genetic modifications.

Dynamics of Protein Damage in Yeast Frataxin Mutant Exposed to Oxidative Stress.

OMICS. 2010 Oct 20. [Epub ahead of print]
Kim JH, Sedlak M, Gao Q, Riley CP, Regnier FE, Adamec J.
Bindley Bioscience Center at Discovery Park, Purdue University , West Lafayette, Indiana.

Keywords: Oxidative stress, protein carbonylation, aging, neurodegenerative disorders, diabetes, cancer, biomarkers, energy metabolism, peroxiredoxin (TSA1), thioredoxin II (TRX2).

Frataxin is an important regulator of iron metabolism

MRC, National Institute for Medical Research, 20 October 2010

Brief summary of the article by Dr. Annalisa Pastore, explaining their research in words more simple and comprehensible to all

Frataxin depletion in yeast triggers upregulation of iron transport systems before affecting iron-sulfur enzyme activities.

J Biol Chem. 2010 Oct 18. [Epub ahead of print]
Moreno-Cermeno A, Obis E, Belli G, Cabiscol E, Ros J, Tamarit J.

University of Lleida, Spain.

Keywords: frataxin, a mitochondrial protein, iron homeostasis, yeast model, frataxin homolog YFH1, aconitase, secondary events, iron overloading, superoxide dismutase, protein carbonyl formation, manganese, metal ion transporter Smf2.

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Pharmacokinetic evaluation of idebenone.

Expert Opin Drug Metab Toxicol. 2010 Nov;6(11):1437-44.

Becker C, Bray-French K, Drewe J.
Basel Pharmacoepidemiology Unit, University Hospital Basel, Switzerland.

Conclusions: Idebenone shows dose-proportional pharmacokinetics in healthy subjects in daily doses up to 2250 mg, and was safe and well tolerated at doses up to 2250 mg/day, in clinical studies.

Pathogenesis of impaired glucose tolerance and diabetes in Friedreich's ataxia: contribution of insulin resistance and pancreatic beta cell dysfunction.

The free library,
Miriam Cnop, MD, PhD, Universite Libre de Bruxelles, Brussels, Belgium

Research summary

Keywords: pancreatic b cells, Friedreich's ataxia, insulin demand.

Structural bases for the interaction of frataxin with the central components of iron–sulphur cluster assembly

Nature Communications, Volume:1, Article number: 95, DOI: doi:10.1038/ncomms1097
Received 08 June 2010, Accepted 22 September 2010, Published 19 October 2010

National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
* Filippo Prischi,
* Clara Iannuzzi,
* Chiara Pastore,
* Salvatore Adinolfi,
* Stephen R. Martin &
* Annalisa Pastore
European Molecular Biology Laboratory, EMBL c/o DESY, Notkestrasse 85, Hamburg D-22603, Germany.
* Petr V. Konarev &
* Dmitri I. Svergun

OPEN ARTICLE

Mitochondrial ROS Generation and Its Regulation: Mechanisms Involved in H2O2 Signaling

Antioxidants & Redox Signaling. Online Ahead of Print: October 18, 2010, doi:10.1089/ars.2010.3363.
Michel Rigoulet, Edgar D. Yoboue, Anne Devin. Université Bordeaux 2, and Institute of Biochemistry and Genetics of the Cell (IBGC) du CNRS, Bordeaux, France.

Keyworsd: Mitochondria, reactive oxygen species, oxidative stress, respiratory chain, dehydrogenases, bc1 complex, complex I, signaling molecules.

Public summary of opinion on orphan designationN-(6-(2-aminophenylamino)-6-oxohexyl)-4-methylbenzamide for the treatment of Friedreich’s ataxia,

12 October 2010
EMA/COMP/455242/2010
Committee for Orphan Medicinal Products.

On 1 October 2010, orphan designation (EU/3/10/793) was granted by the European Commission to Repligen Europe Limited, Ireland, for N-(6-(2-aminophenylamino)-6-oxohexyl)-4-methylbenzamide for the treatment of Friedreich’s ataxia.

Induced pluripotency: history, mechanisms, and applications

Genes & Dev. 2010. 24: 2239-2263, doi: 10.1101/gad.1963910
Matthias Stadtfeld, Konrad Hochedlinger

(REVIEWS)

OPEN ACCESS

The generation of induced pluripotent stem cells (iPSCs) from somatic cells demonstrated that adult mammalian cells can be reprogrammed to a pluripotent state by the enforced expression of a few embryonic transcription factors.

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In vivo evidence for the iron binding activity of an iron-sulfur cluster assembly protein IscA in Escherichia co

Biochem. J. (2010) Immediate Publication, doi:10.1042/BJ20101507

Wu Wang, Hao Huang, Guoqiang Tan, Fan Si, Min Liu, Aaron P. Landry, Jianxin Lu and Huangen Ding
Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, U.S.A.

"IscU, a proposed iron-sulfur cluster assembly scaffold protein, and CyaY, a bacterial frataxin homolog that has been postulated as an iron donor for the iron-sulfur cluster assembly, fail to bind any iron in E. coli cells under the same experimental conditions"

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Epigenetic modifications and human disease

Nature Biotechnology, Volume:28, Pages:1057–1068,Year published:(2010)
DOI:10.1038/nbt.1685, Published online 13 October 2010

Anna Portela & Manel Esteller
Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.
Manel Esteller
Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.

Epigenetic modifications in neurodegenerative and neurological diseases (Friedreich's ataxia) , Epigenetic modifications in neurodevelopmental disorder

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Epigenetic modifications as therapeutic targets

Nature Biotechnology, Volume: 28 ,Pages: 1069–1078,Year published:(2010)
DOI:10.1038/nbt.1678, Published online 13 October 2010

Theresa K Kelly, Daniel D De Carvalho & Peter A Jones Departments of Urology and Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

The paper focus on recent examples in which epigenetic modifications have been used to evaluate disease risk, progression and clinical response. It provide a broad overview of the accomplishments, remaining challenges and unrealized potential of epigenetic therapies in a range of diseases, with a particular emphasis on cancer.

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On the Trail of the Epigenetic Code: Test System on Drosophila Should Provide the Key to Histone Function

ScienceDaily (Oct. 12, 2010) — Test system on Drosophila should provide the key to histone function. The genetic inherited material DNA was long viewed as the sole bearer of hereditary information. The function of its packaging proteins, the histones, was believed to be exclusively structural. Additional genetic information can be stored, however, and passed on to subsequent generations through chemical changes in the DNA or histones. read more

Original paper: A genetic system to assess in vivo the functions of histones and histone modifications in higher eukaryotes

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Kinematic analysis of lingual movements during consonant productions in dysarthric speakers with Friedreich's ataxia: A case-by-case analysis.

Clin Linguist Phon. 2010 Oct 8. [Epub ahead of print]

Folker JE, Murdoch BE, Cahill LM, Delatycki MB, Corben LA, Vogel AP.

School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, QLD, Australia.

An in Vivo Method for Characterization of Protein Interactions within Sulfur Trafficking Systems of E. coli

J. Proteome Res., Just Accepted Manuscript, DOI: 10.1021/pr100920r
Publication Date (Web): October 11, 2010

Heather May Bolstad and Matthew James Wood

KEYWORDS: iron-sulfur clusters, in vivo method, mass spectrometry, iron-sulfur biogenesis, general tool for the determination of sulfur trafficking mechanisms.

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Dizziness in Orthopaedic Physical Therapy Practice: History and Physical Examination

The Journal of Manual & Manipulative Therapy
Vol. 13 No. 4 (2005), 222 - 251

Paul Vidal, PT, MHSc, DPT, OCS, MTC
Peter Huijbregts, PT, MSc, MHSc, DPT, OCS, MTC, FAAOMPT, FCAMT


Physical therapy (PT) differential diagnosis of patients complaining of dizziness centers on distinguishing those patients who might benefit from sole management by the physical therapist from those patients who require referral for medical-surgical differential diagnosis and (co) management.....

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Microchip Technology Rapidly Identifies Compounds for Regrowing Nerves in Live Animals

ScienceDaily (Oct. 11, 2010) — Scientists have long sought the ability to regenerate nerve cells, or neurons, which could offer a new way to treat spinal-cord damage as well as neurological diseases such as Alzheimer's or Parkinson's. Many chemicals can regenerate neurons grown in Petri dishes in the lab, but it's difficult and time-consuming to identify those chemicals that work in live animals, which is critical for developing drugs for humans. read more

Evaluation of neuropsychological functions in patients with Friedreich ataxia before and after cognitive therapy

Funct Neurol. 2010 Apr-Jun;25(2):81-5.
Ciancarelli I, Cofini V, Carolei A.

Keywords: Friedreich ataxia (FA, severe disability, cognitive functions, mood disorders, conflicting results, role of cognitive rehabilitation therapy, MMSE, Rey 15-item Memorization Test, Raven's Colored Progressive Matrices, the Phonemic Verbal Fluency Test, the Symbol Digit Modalities Test, Zung scale.

Remarkably Efficient New Method For Generating Human Stem Cells

Medical News Today, Article Date: 02 Oct 2010 - 0:00 PDT

The ability to efficiently generate patient-specific stem cells from differentiated cells and then reliably direct them to form specialized cells (like neurons or muscle) has tremendous therapeutic potential for replacing diseased or damaged tissues... read more


Technology Review, Friday, October 1, 2010

A New Way to Make Stem Cells

Using RNA instead of DNA could avoid the health risks--and the political pitfalls--of stem-cell treatments.

A Harvard researcher has developed a way to make pluripotent stem cells that solves several of the major impediments to using them to treat human diseases. read more...

Normal and Friedreich ataxia cells express different isoforms of frataxin with complementary roles in iron-sulfur cluster assembly.

J Biol Chem. 2010 Oct 2. [Epub ahead of print]

Gakh O, Bedekovics T, Duncan SF, Smith DY 4th, Berkholz DS, Isaya G.
Mayo Clinic, United States.

Keywords: frataxin (FXN), Fe-S cluster, FXN mRNA, FXN42-210, FXN81-210, levels of both isoforms are relevant, FXN81-210/FXN42-210 molar ratio, replacement therapies.

PGC-1 Coactivators in Cardiac Development and Disease

Circulation Research. 2010;107:825-838
doi: 10.1161/CIRCRESAHA.110.223818

Daniel P. Kelly, Guest Editor
Glenn C. Rowe, Aihua Jiang, Zolt Arany

From the Cardiovascular Institute at the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.

Key Words: PGC-1 • metabolism • heart failure • mitochondria