A role for p53 in mitochondrial stress response control of longevity in C. elegans.

Exp Gerontol. 2010 Feb 18. [Epub ahead of print]

Torgovnick A, Schiavi A, Testi R, Ventura N.
Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata", Rome, Italy.

Keywords: aging, degenerative disorders, mitochondrial deterioration, cellular damage accumulation, mitochondrial dysfunction, electron transport chain, p53/cep-1, frataxin, Friedreich's ataxia, antioxidant glutathione-S-transferase, therapeutic approaches.

Repeat instability as the basis for human diseases and as a potential target for therapy

Nature Reviews Molecular Cell Biology 11, 165-170 (March 2010) | doi:10.1038/nrm2854

Arturo López Castel1, John D. Cleary1,2 & Christopher E. Pearson1,2
1. Arturo López Castel, John D. Cleary and Christopher E. Pearson are at the Program of Genetics & Genome Biology, The Hospital for Sick Children, 101 College Avenue, East Tower 15-312, TMDT Toronto, Ontario, Canada, M5G 1L7.
2. John D. Cleary and Christopher E. Pearson are also at the Department of Molecular Genetics, University of Toronto, Canada.

Keywords: Expansions of repetitive DNA sequences, neurological, neuromuscular diseases, DNA replication, repair, recombination, transcription, epigenetics, therapeutic strategies,Huntington's disease (HD), myotonic dystrophy (DM1), fragile X syndrome type A (FRAXA), Friedreich's ataxia (FRDA), spinocerebellar ataxias (SCAs)

Structure and Organization of Mitochondrial Respiratory Complexes: A New Understanding of an Old Subject

Antioxidants & Redox Signaling. Ahead of print. doi:10.1089/ars.2009.2704.

Giorgio Lenaz and Maria Luisa Genova
Dipartimento di Biochimica “G. Moruzzi,” Alma Mater Studiorum, Università di Bologna, Bologna, Italy.
 
Keywords: enzymatic complexes, mitochondrial respiratory chain,  redox potential, (complexes I, III, and IV), reactive oxygen species, smaller redox components, coenzyme Q, cytochrome c, supramolecular associations, substrate channeling, oxygen radical formation. .

Potential Therapeutic Benefits of Strategies Directed to Mitochondria

Antioxidants & Redox Signaling. -Not available-, ahead of print. doi:10.1089/ars.2009.2788.

Amadou K.S. Camara,1
Edward J. Lesnefsky,5,6 and
David F. Stowe1,2,3,4
1Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
2Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
3Department of Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin.
4Research Service, Veterans Affairs Medical Center, Milwaukee, Wisconsin.
5Medical Service, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia.
6Departments of Medicine (Division of Cardiology) and Biochemistry, Virginia Commonwealth University, Richmond, Virginia.

Mechanisms of brain iron transport: insight into neurodegeneration and CNS disorders

Eric Mills‌1, Xian-ping Dong‌1, Fudi Wang‌2 & Haoxing Xu‌1†
1Department of Molecular, Cellular, and Developmental Biology, University of Michigan, 3089 Natural Science Building (Kraus), 830 North University, Ann Arbor, MI 48109, USA. haoxingx@umich.edu
2Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China
 
Keywords: iron, copper, zinc, manganese, cobalt, iron-transport mechanisms in the CNS,  neurodegeneration ,CNS iron homeostasis, blood–brain barrier, novel therapeutic targets.

Atypical, perhaps under-recognized? An unusual phenotype of Friedreich ataxia

Neurogenetics, 10.1007/s10048-009-0233-x

Beate Diehl1, Michael S. Lee2, Janet R. Reid3, Craig D. Nielsen4 and Marvin R. Natowicz5, 6 Contact Information
(1) National Hospital for Neurology and Neurosurgery, London, UK
(2) Department of Ophthalmology, University of Minnesota, Minneapolis, MN, USA
(3) Radiology Institute, Cleveland Clinic, Cleveland, OH, USA
(4) Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
(5) Genomic Medicine Institute, NE-5 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
(6) Institutes of Pathology and Laboratory Medicine, Neurology and Pediatrics, Cleveland Clinic, Cleveland, OH, USA

Received: 3 August 2009 Accepted: 29 December 2009 Published online: 17 February 2010

Keywords Atypical Friedreich ataxia - Variant Friedreich ataxia - Frataxin - Mitochondrial - Optic atrophy

FRIEDREICH'S ATAXIA: MOLECULAR MECHANISMS, REDOX CONSIDERATIONS AND THERAPEUTIC OPPORTUNITIES

Antioxid Redox Signal. 2010 Feb 16.

Santos R, Lefevre S, Sliwa D, Seguin A, Camadro JM, Lesuisse E.
Institut Jacques Monod, Mitochondria, Metals and Oxidative Stress Laboratory, Bât.Buffon, 15 rue Hélène Brion, Paris, France, 75013, +331 57 27 80 28, +331 57 27 81 01; santos.renata@ijm.univ-paris-diderot.fr.

Keywords: Mitochondrial dysfunction, oxidative damage, neurodegenerative diseases,  Alzheimer's,  Parkinson's,  Friedreich's ataxia (FRDA),  GAA trinucleotide repeat expansion, FXN,  frataxin,  respiration, iron-sulfur cluster assembly, iron homeostasis, maintenance of the redox status, therapeutic approaches.

Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery

Blood, 28 January 2010, Vol. 115, No. 4, pp. 860-869.

Daniel R. Crooks1,2, Manik C. Ghosh2, Ronald G. Haller3, Wing-Hang Tong2, and Tracey A. Rouault2


1 Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC; 2 Molecular Medicine Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; and 3 Department of Neurology, University of Texas Southwestern Medical Center and Veterans Administration North Texas Medical Center, and Neuromuscular Center, Institute for Exercise and Environmental Medicine, Dallas

Keywords:  ferrochelatase, iron-sulfur [2Fe-2S] cluster, posttranscriptional regulation of ferrochelatase,  in vivo.  We propose that decreased heme biosynthesis resulting from impaired Fe-S cluster assembly can contribute to the pathogenesis of diseases caused by defective Fe-S cluster biogenesis.

R loops stimulate genetic instability of CTG·CAG repeats

PNAS, Edited by Philip C. Hanawalt, Stanford University, Stanford, CA, and approved November 27, 2009 (received for review August 26, 2009)

Yunfu Lina, Sharon Y. R. Dentb, John H. Wilsona, Robert D. Wellsc, and Marek Napieralab,c,1

aBaylor College of Medicine, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, One Baylor Plaza, Houston, TX 77030;
bUniversity of Texas M. D. Anderson Cancer Center, Department of Biochemistry and Molecular Biology and Center for Cancer Epigenetics, 1515 Holcombe Boulevard, Houston, TX 77030; and
cCenter for Genome Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, 2121 West Holcombe Boulevard, Houston, TX 77030.
 
This article contains supporting information online at www.pnas.org/cgi/content/full/0909740107/DCSupplemental.

Safety issues of iron chelation therapy in patients with normal range iron stores including thalassaemia, neurodegenerative, renal and infectious diseases

Expert Opinion on Drug Safety. Posted online on 09 Jan 2010.

G J Kontoghiorghes‌†1, A Kolnagou‌2, C-T Peng‌3, S V Shah‌4 & A Aessopos‌5
1Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3 Ammochostou Sreet, Limassol, 3021. Cyprus+35 7 2627 2076; +35 72 627 1434; kontoghiorghes.g.j@pri.ac.cy
2Postgraduate Research Institute, Science, Technology, Environment and Medicine Limassol and Thalassaemia unit, Paphos General Hospital, Paphos, Cyprus
3Children's Medical Center, China Medical University Hospital, Taichung, Taiwan
4Division of Nephrology, University of Arkansas for Medical Sciences, Little Rock, USA
5First Department of Internal Medicine, University of Athens Medical School, Laiko Hospital, Athens, Greece

Keywords: thalassaemia,  chelation therapy, body iron levels,  neurodegenerative, renal, infectious diseases, chelator overdose toxicity, essential metal deficiencies, deferoxamine, deferasirox,  deferiprone, short-term treatments,  longer term treatments,  non-iron loading conditions.

Immunobiology of gene therapy for neurodegenerative disease: prospects and risks

Gene Therapy advance online publication 11 February 2010; doi: 10.1038/gt.2010.2

M M McMenamin1 and M J A Wood
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

Keywords: viral vectors, neurodegenerative disease, immune response, CNS, re-administration

New hope in hunt for ataxia cure

theage.com.au
6:22AM Thu February 11, 2010

NICK MILLER -february 11, 2010  

Teams from the University of Melbourne and the Monash Institute of Medical Research have made pluripotent stem cells from the skin of FA sufferers, .....read more

Frataxin, a molecule of mystery: trading stability for function in its iron-binding site

Biochem. J. (2010) 426 (e1–e3) (Printed in Great Britain)

Darius J. R. Lane* and Des R. Richardson†1
*Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, Victoria, 3800, Australia, and †Department of Pathology and Bosch Institute, Iron Metabolism and Chelation Program, Blackburn Building, University of Sydney, Sydney, New South Wales, 2006, Australia
 
Key words: frataxin, Friedreich's ataxia (FRDA), iron–sulfur cluster, Isu protein, mitochondrion, yeast frataxin (Yfh1).

Overcoming frataxin gene silencing in Friedreich’s ataxia with small molecules: studies on cellular and animal models

Rai, Myriam.
F204 - Faculté de médecine - Sciences biomédicales
Doctorat en sciences biomédicales, Date de défense 2010-01-05
Keywords: frataxin, Friedreich's ataxia, chromatin, biomarker, histone deacetylase inhibitor.

Diazoxide for the treatment of Friedreich's Ataxia

United States Patent Application 20100029576 Kind Code:A1

Inventors: Marobbio, Carlo Marya Thomas (Bari, IT) , Palmeri, Luigi (Bari, IT),  Palmeri, Ferdinando (Bari, IT),  Santoro, Antonella (Bari, IT)

Assignee: UNIVERSITA' DEGLI STUDI DI BARI (Bari, IT)

"A pharmaceutical preparation treats Friedreich's ataxia and treats or prevents pathologies related thereto"

"With the present invention it is therefore possible to increase the frataxin expression level."

Pearls: Myelopathy

Semin Neurol. 2010 Feb;30(1):38-43. Epub 2010 Feb 1.

Kumar N.
Department of Neurology, Mayo Clinic, Rochester, Minnesota.

Keywords: disorders of the spinal cord, neuroimaging, serum antibody marker,  demyelinating disease,  multiple sclerosis, acquired copper deficiency,  vitamin B (12) deficiency,  hereditary myelopathies, Friedreich's ataxia, spastic paraparesis, leukodystrophy phenotype, adrenomyeloneuropathy.

Clinical Guidelines on Best Practice

Charity rolls out new ataxia guidelines
National guidelines have been launched for the treatment and care of ataxia. The 50-page guidelines are now available free of charge from national charity Ataxia UK.

“Although more than 10,000 people in the UK have a type of ataxia, many doctors and medical professionals may not be aware of the condition or how to treat it,” said Dr Liz Harrison, Chair of Ataxia UK.

“From what our members tell us, there is a big need for the guidelines. Covering a wide range of topics including genetic testing, occupational therapy, and palliative care, we hope that any professionals with an interest in ataxia will take up the offer of a free copy.”

The guidelines have been drawn up with the help of neurologists, geneticists, and experts in other disciplines including speech and language therapy and physiotherapy. For the first time the guidelines have a section on occupational therapy that is accredited by the College of Occupational Therapy.

Dr Harrison said, “Improving treatment and care for people with ataxia is one of our main aims as a charity, along with funding research and supporting people who live with the condition. Although we are not a big charity, we believe the professional standard of our new guidelines shows that smaller groups can still influence and improve care.’

Ataxia UK also aims to roll out a system of accredited Ataxia Centres round the UK, and has just opened the third in Oxford. The model offers specialist clinics with neurologists and support from a dedicated Ataxia Nurse, with the aim of providing integrated care and referrals for ataxia patients.

Notes
• Ataxia means ‘lack of order’. People with ataxia have a type of degenerative neurological disorder that affects walking, speech, and co-ordination. Over 10,000 people in the UK have ataxia and there is currently no cure. A recent study showed that just 7% of the public know what ataxia is.
• Ataxia UK is the national charity for people affected by ataxia, providing support services and funding ground-breaking research. In the past five years they have spent over £3 million on research into treatments and a possible cure for ataxia, with several important breakthroughs. Charity no: 1102391 www.ataxia.org.uk
• Guidelines for the management and treatment of ataxia are available now from Ataxia UK, contact 020 7582 1444 or email research@ataxia.org.uk

For more information please Claire McGowan on 020 7587 3925 mob 0779 2214508 email cmcgowan@ataxia.org.uk

Neuropatía auditiva, diagnóstico y manejo audiológico - Auditory neuropathy / dyssychrony, assessment and audiologic management

Rev. Otorrinolaringol. Cir. Cabeza Cuello 2009; 69: 271-280,

Oscar Cañete S1.
1 Tecnólogo Médico, Servicio de Otorrinolaringología, Hospital Padre Hurtado.

Palabras clave: Neuropatía auditiva, des sincronía auditiva, desorden del espectro de neuropatía auditiva, hipoacusia neural, hipoacusia en neonatos de riesgo, potenciales evocados de tronco, ataxia de Friedreich, Charcot-Marie-Tooth.

Keywords: Auditory neuropathy, Neural hearing loss, Auditory evoked potentials, Auditory Dyssynchrony. Hearing loss in high risk newborns, Friedreich's ataxia, Charcot-Marie-Tooth.

FULL TEXT (Spanish)

Rapid determination of tricarboxylic acid cycle enzyme activities in biological samples

BMC Biochemistry 2010, 11:5doi:10.1186/1471-2091-11-5
Sergio Goncalves , Vincent Paupe , Emmanuel P Dassa , Jean-Jacques Briere , Judith Favier , Anne-Paule Gimenez-Roqueplo , Paule Benit and Pierre Rustin


Published: 28 January 2010

OPEN ACCES

Abstract (provisional)

Background

In the last ten years, deficiencies in tricarboxylic acid cycle (TCAC) enzymes have been shown to cause a wide spectrum of human diseases, including malignancies and neurological and cardiac diseases. A prerequisite to the identification of disease-causing TCAC enzyme deficiencies is the availability of effective enzyme assays.

Results

We developed three assays that measure the full set of TCAC enzymes. One assay relies on the sequential addition of reagents to measure succinyl-CoA ligase activity, followed by succinate dehydrogenase, fumarase and, finally, malate dehydrogenase. Another assay measures the activity of -ketoglutarate dehydrogenase followed by aconitase and isocitrate dehydrogenase. The remaining assay measures citrate synthase activity using a standard procedure. We used these assays successfully on extracts of small numbers of human cells displaying various severe or partial TCAC deficiencies and on frozen heart homogenates from heterozygous mice harboring an SDHB gene deletion.

Conclusion

This set of assays is rapid and simple to use and can immediately detect even partial defects, as the activity of each enzyme can be readily compared with one or more other activities measured in the same sample.

FULL TEXT (pdf)