Sunday, October 31, 2010

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.

Friday, October 29, 2010

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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Thursday, October 28, 2010

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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Wednesday, October 27, 2010

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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Tuesday, October 26, 2010

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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Sunday, October 24, 2010

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.