Can J Neurol Sci. 2009 Jul;36(4):409-28.
Finsterer J.
Krankenanstalt Rudolfstiftung, Vienna, Austria, Europe.
Keywors: Heredoataxias, genetic disorders, cerebellar syndrome, inheritance, autosomal dominant, autosomal recessive, X-linked, and maternally inherited heredoataxias, Friedreich ataxia.
Wednesday, August 5, 2009
New clues about vitamin D functions in the nervous system
by: E. Garcion, N. Wionbarbot, C. Monteromenei, F. Berger, D. Wion
Trends in Endocrinology and Metabolism, Vol. 13, No. 3. (01 April 2002), pp. 100-105.
Keywords: 1α,25 dihydroxyvitamin D 3 [1,25-(OH) 2 D 3 ], brain function, nuclear receptor, neurons, glial cells, neurotrophic factors, neurotransmitter synthesis, nitric oxide synthase, increase glutathione levels, brain detoxification pathways, neuroprotective, immunomodulatory effects, neurodegenerative diseases, neuroimmune diseases, glioma cell death, brain tumors.
Other link: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3K-45BCJ53-7&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=36fe7df09fbacd4b33fe816072a1793d
Trends in Endocrinology and Metabolism, Vol. 13, No. 3. (01 April 2002), pp. 100-105.
Keywords: 1α,25 dihydroxyvitamin D 3 [1,25-(OH) 2 D 3 ], brain function, nuclear receptor, neurons, glial cells, neurotrophic factors, neurotransmitter synthesis, nitric oxide synthase, increase glutathione levels, brain detoxification pathways, neuroprotective, immunomodulatory effects, neurodegenerative diseases, neuroimmune diseases, glioma cell death, brain tumors.
Other link: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3K-45BCJ53-7&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=36fe7df09fbacd4b33fe816072a1793d
Abnormal Brain Circuits May Prevent Movement Disorder
ScienceDaily (Aug. 4, 2009)
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Standaert says that although dystonia is a relatively rare disorder, the study has implications for other neurological illnesses, such as Parkinson's, Alzheimer's, and Huntington's diseases; ataxia and muscular dystrophies; and even forms of migraine.
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Source: The Journal of Neuroscience, August 5, 2009, 29(31):9740-9747; doi:10.1523/JNEUROSCI.2300-09.2009
Cerebellothalamocortical Connectivity Regulates Penetrance in Dystonia
.../...
Standaert says that although dystonia is a relatively rare disorder, the study has implications for other neurological illnesses, such as Parkinson's, Alzheimer's, and Huntington's diseases; ataxia and muscular dystrophies; and even forms of migraine.
.../...
Source: The Journal of Neuroscience, August 5, 2009, 29(31):9740-9747; doi:10.1523/JNEUROSCI.2300-09.2009
Cerebellothalamocortical Connectivity Regulates Penetrance in Dystonia
1Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York 11030, Departments of 2Neurology and 3Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, 4Department of Radiology, Weill Cornell Medical College, New York, New York 10065, and 5Mirken Department of Neurology, Beth Israel Medical Center, New York, New York 10003
Tuesday, August 4, 2009
Deficiency in frataxin homologue YFH1 in the yeast Pichia guilliermondii leads to missregulation of iron acquisition and riboflavin biosynthesis and a
Biometals. 2009 Aug 1.
Pynyaha YV, Boretsky YR, Fedorovych DV, Fayura LR, Levkiv AI, Ubiyvovk VM, Protchenko OV, Philpott CC, Sibirny AA.
Deficiency in frataxin homologue YFH1 in the yeast Pichia guilliermondii leads to missregulation of iron acquisition and riboflavin biosynthesis and affects sulfate assimilation.
Pynyaha YV, Boretsky YR, Fedorovych DV, Fayura LR, Levkiv AI, Ubiyvovk VM, Protchenko OV, Philpott CC, Sibirny AA.
Institute of Cell Biology, NAS of Ukraine, Drahomanov Street 14/16, 79005, Lviv, Ukraine.
Keyword: riboflavin, YFH1, frataxin homologue, iron, impaired sulfate assimilation, hypersensitivity to hydrogen peroxide, superoxide dismutase.
Frataxin, an iron taxi on the road to cellular Fe–S bioassembly
Traffic and storage of metal ions, J Biol Inorg Chem (2009) 14 (Suppl 1):S53–S56 (Oral Presentation)
G-08
Frataxin, an iron taxi on the road to cellular Fe–S bioassembly
Timothy L. Stemmler
Department of Biochemistry and Molecular Biology, Wayne State
University, School of Medicine, Detroit, MI 48201 USA.
tstemmle@med.wayne.edu
http://www.springerlink.com/content/8x412685h746427g/fulltext.pdf
Keywords: Friedreich’s ataxia, iron homeostasis, iron overload, oxidative stress, mitochondrial DNA stability, iron–sulfur protein, iron chaperone, acidic residues, Fe–S cluster assembly enzyme (Isu),
G-08
Frataxin, an iron taxi on the road to cellular Fe–S bioassembly
Timothy L. Stemmler
Department of Biochemistry and Molecular Biology, Wayne State
University, School of Medicine, Detroit, MI 48201 USA.
tstemmle@med.wayne.edu
http://www.springerlink.com/content/8x412685h746427g/fulltext.pdf
Keywords: Friedreich’s ataxia, iron homeostasis, iron overload, oxidative stress, mitochondrial DNA stability, iron–sulfur protein, iron chaperone, acidic residues, Fe–S cluster assembly enzyme (Isu),
Friday, July 31, 2009
Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis
This study is currently recruiting participants.
Verified by National Institutes of Health Clinical Center (CC), July 2009
First Received: July 30, 2009
Objective: The goal of this study is to assess the safety, therapeutic efficacy and mechanism of action of idebenone in primary-progressive multiple sclerosis (PP-MS) patients
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Verified by National Institutes of Health Clinical Center (CC), July 2009
First Received: July 30, 2009
Objective: The goal of this study is to assess the safety, therapeutic efficacy and mechanism of action of idebenone in primary-progressive multiple sclerosis (PP-MS) patients
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Thursday, July 30, 2009
Scientists discover why we never forget how to ride a bicycle
PhysOrg.com, July 17th, 2009
Their research, published this month in Nature Neuroscience, has identified a key nerve cell in the brain that controls the formation of memories for motor skills such as riding a bicycle, skiing or eating with chop sticks.
Keywords: cerebellum, brain, co-ordinated movement, molecular layer interneuron, motor skill, brain-computer interfaces, prosthetic devices.
Their research, published this month in Nature Neuroscience, has identified a key nerve cell in the brain that controls the formation of memories for motor skills such as riding a bicycle, skiing or eating with chop sticks.
Keywords: cerebellum, brain, co-ordinated movement, molecular layer interneuron, motor skill, brain-computer interfaces, prosthetic devices.
Wednesday, July 29, 2009
Structural basis for the mechanism of respiratory complex I.
J Biol Chem. 2009 Jul 27.
Medical Research Council, United Kingdom.
Keywords: Cellular energy production, human neurodegenerative diseases, frataxin, Fe-S clusters, cysteines, Mitochondrial complex I, reactive oxygen species (ROS), iron-binding sites .
Tuesday, July 28, 2009
Stress signals link pre-existing sickness with susceptibility to bacterial infection
Bio-Medicine, Date:7/28/2009
Mitochondrial diseases disrupt the power generating machinery within cells and increase a person's susceptibility to bacterial infection, particularly in the lungs or respiratory tract.
Mitochondrial diseases disrupt the power generating machinery within cells and increase a person's susceptibility to bacterial infection, particularly in the lungs or respiratory tract.
Friday, July 24, 2009
The First Cellular Models Based on Frataxin Missense Mutations That Reproduce Spontaneously the Defects Associated with Friedreich Ataxia
Open-access -Creative Commons Attribution License
Full text
PLoS One. 2009; 4(7): e6379.
Published online 2009 July 24. doi: 10.1371/journal.pone.0006379.
The First Cellular Models Based on Frataxin Missense Mutations That Reproduce Spontaneously the Defects Associated with Friedreich Ataxia
Nadège Calmels,#1,4,5 Stéphane Schmucker,#1,4,5 Marie Wattenhofer-Donzé,1,5 Alain Martelli,1,5 Nadège Vaucamps,1 Laurence Reutenauer,1,3 Nadia Messaddeq,1,2 Cécile Bouton,6 Michel Koenig,1,2,3,4,5 and Hélène Puccio1,2,3,4,5*
1IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Illkirch, France
2Inserm, U596, Illkirch, France
3CNRS, UMR7104, Illkirch, France
4Université de Strasbourg, Strasbourg, France
5Collège de France, Chaire de génétique humaine, Illkirch, France
6Institut de Chimie des Substance Naturelles, CNRS, Gif-sur-Yvette, France
Ellen A. A. Nollen, Editor
University Medical Center Groningen, Netherlands
#Contributed equally.
* E-mail:hpuccio@igbmc.fr
Conceived and designed the experiments: NC SS HMP. Performed the experiments: NC SS MWD AM NV LR NM CB. Analyzed the data: NC SS HMP. Wrote the paper: NC SS AM MK HMP.
Received May 11, 2009; Accepted June 25, 2009.
ABSTRACT
Background
Friedreich ataxia (FRDA), the most common form of recessive ataxia, is due to reduced levels of frataxin, a highly conserved mitochondrial iron-chaperone involved in iron-sulfur cluster (ISC) biogenesis. Most patients are homozygous for a (GAA)n expansion within the first intron of the frataxin gene. A few patients, either with typical or atypical clinical presentation, are compound heterozygous for the GAA expansion and a micromutation.
Methodology
We have developed a new strategy to generate murine cellular models for FRDA: cell lines carrying a frataxin conditional allele were used in combination with an EGFP-Cre recombinase to create murine cellular models depleted for endogenous frataxin and expressing missense-mutated human frataxin. We showed that complete absence of murine frataxin in fibroblasts inhibits cell division and leads to cell death. This lethal phenotype was rescued through transgenic expression of human wild type as well as mutant (hFXNG130V and hFXNI154F) frataxin. Interestingly, cells expressing the mutated frataxin presented a FRDA-like biochemical phenotype. Though both mutations affected mitochondrial ISC enzymes activities and mitochondria ultrastructure, the hFXNI154F mutant presented a more severe phenotype with affected cytosolic and nuclear ISC enzyme activities, mitochondrial iron accumulation and an increased sensitivity to oxidative stress. The differential phenotype correlates with disease severity observed in FRDA patients.
Conclusions
These new cellular models, which are the first to spontaneously reproduce all the biochemical phenotypes associated with FRDA, are important tools to gain new insights into the in vivo consequences of pathological missense mutations as well as for large-scale pharmacological screening aimed at compensating frataxin deficiency.
Full text
PLoS One. 2009; 4(7): e6379.
Published online 2009 July 24. doi: 10.1371/journal.pone.0006379.
The First Cellular Models Based on Frataxin Missense Mutations That Reproduce Spontaneously the Defects Associated with Friedreich Ataxia
Nadège Calmels,#1,4,5 Stéphane Schmucker,#1,4,5 Marie Wattenhofer-Donzé,1,5 Alain Martelli,1,5 Nadège Vaucamps,1 Laurence Reutenauer,1,3 Nadia Messaddeq,1,2 Cécile Bouton,6 Michel Koenig,1,2,3,4,5 and Hélène Puccio1,2,3,4,5*
1IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), Illkirch, France
2Inserm, U596, Illkirch, France
3CNRS, UMR7104, Illkirch, France
4Université de Strasbourg, Strasbourg, France
5Collège de France, Chaire de génétique humaine, Illkirch, France
6Institut de Chimie des Substance Naturelles, CNRS, Gif-sur-Yvette, France
Ellen A. A. Nollen, Editor
University Medical Center Groningen, Netherlands
#Contributed equally.
* E-mail:hpuccio@igbmc.fr
Conceived and designed the experiments: NC SS HMP. Performed the experiments: NC SS MWD AM NV LR NM CB. Analyzed the data: NC SS HMP. Wrote the paper: NC SS AM MK HMP.
Received May 11, 2009; Accepted June 25, 2009.
ABSTRACT
Background
Friedreich ataxia (FRDA), the most common form of recessive ataxia, is due to reduced levels of frataxin, a highly conserved mitochondrial iron-chaperone involved in iron-sulfur cluster (ISC) biogenesis. Most patients are homozygous for a (GAA)n expansion within the first intron of the frataxin gene. A few patients, either with typical or atypical clinical presentation, are compound heterozygous for the GAA expansion and a micromutation.
Methodology
We have developed a new strategy to generate murine cellular models for FRDA: cell lines carrying a frataxin conditional allele were used in combination with an EGFP-Cre recombinase to create murine cellular models depleted for endogenous frataxin and expressing missense-mutated human frataxin. We showed that complete absence of murine frataxin in fibroblasts inhibits cell division and leads to cell death. This lethal phenotype was rescued through transgenic expression of human wild type as well as mutant (hFXNG130V and hFXNI154F) frataxin. Interestingly, cells expressing the mutated frataxin presented a FRDA-like biochemical phenotype. Though both mutations affected mitochondrial ISC enzymes activities and mitochondria ultrastructure, the hFXNI154F mutant presented a more severe phenotype with affected cytosolic and nuclear ISC enzyme activities, mitochondrial iron accumulation and an increased sensitivity to oxidative stress. The differential phenotype correlates with disease severity observed in FRDA patients.
Conclusions
These new cellular models, which are the first to spontaneously reproduce all the biochemical phenotypes associated with FRDA, are important tools to gain new insights into the in vivo consequences of pathological missense mutations as well as for large-scale pharmacological screening aimed at compensating frataxin deficiency.
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