Haque A, Polcyn R, Matzelle D, Banik NL. Brain Sci. 2018 Feb;8(2) . doi:10.3390/brainsci8020033. PMID: 29463007; PMCID: PMC5836052.
Elevated NSE is thought to be a marker of oxidative damage and is the underlying parameter of several neurodegenerative disorders, including Huntington disease (HD), Friedreich ataxia, hereditary spastic paraplegia, rare familial forms Parkinson disease (PD), Alzheimer disease (AD), and amyotrophic lateral sclerosis (ALS).
Regulation of NSE via Cat X or other avenues may be important therapeutic strategies for prevention of inflammation and neurodegeneration in SCI and many other neurodegenerative diseases. Future studies should focus on the regulation of NSE for optimum attenuation of neuro-inflammation and promotion of neuroprotection in neurodegenerative conditions.
Sunday, March 11, 2018
Saturday, March 10, 2018
Pitfalls in molecular diagnosis of Friedreich ataxia
Giulia Barcia, Myriam Rachid, Maryse Magen, Zahra Assouline, Michel Koenig, Benoit Funalot, Christine Barnerias, Agnès Rötig, Arnold Munnich, Jean-Paul Bonnefont, Julie Steffann, European Journal of Medical Genetics, Available online 9 March 2018, ISSN 1769-7212, doi:10.1016/j.ejmg.2018.03.004.
We report on an initial pitfall in the molecular characterization of a 15 year-old girl with Freidreich ataxia (FRDA) who carried a rare deletion in intron 1 of the FXN gene. Due to this deletion TP-PCR failed to amplify the GAA expansion. This exceptional configuration induced misinterpretation of the molecular defect in this patient, who was first reported as having no FXN expansion. NGS analysis of a panel of 212 genes involved in nuclear mitochondrial disorders further revealed an intragenic deletion encompassing exons 4–5 of the FXN gene. Modified TP-PCR analysis confirmed the presence of a classical (GAA)n expansion located in trans. This case points out the possible pitfalls in molecular diagnosis of FRDA in affected patients and their relatives: detection of the FXN expansion may be impaired by several non-pathological or pathological variants around the FXN (GAA)n repeat. We propose a new molecular strategy to accurately detect expansion by TP-PCR in FRDA patients.
We report on an initial pitfall in the molecular characterization of a 15 year-old girl with Freidreich ataxia (FRDA) who carried a rare deletion in intron 1 of the FXN gene. Due to this deletion TP-PCR failed to amplify the GAA expansion. This exceptional configuration induced misinterpretation of the molecular defect in this patient, who was first reported as having no FXN expansion. NGS analysis of a panel of 212 genes involved in nuclear mitochondrial disorders further revealed an intragenic deletion encompassing exons 4–5 of the FXN gene. Modified TP-PCR analysis confirmed the presence of a classical (GAA)n expansion located in trans. This case points out the possible pitfalls in molecular diagnosis of FRDA in affected patients and their relatives: detection of the FXN expansion may be impaired by several non-pathological or pathological variants around the FXN (GAA)n repeat. We propose a new molecular strategy to accurately detect expansion by TP-PCR in FRDA patients.
Friday, March 9, 2018
Molecular genetic testing for hereditary ataxia-What every neurologist should know
Stephanie E. Wallace, Thomas D. Bird Neurology: Clinical Practice Feb 2018, 8 (1) 27-32; DOI: 10.1212/CPJ.0000000000000421
The majority of individuals with hereditary ataxias have nucleotide repeat expansions, pathogenic variants that are not detectable with clinical exome sequencing. Multigene panels that include specific assays to determine nucleotide repeat lengths should be considered first in individuals with hereditary ataxia.
The majority of individuals with hereditary ataxias have nucleotide repeat expansions, pathogenic variants that are not detectable with clinical exome sequencing. Multigene panels that include specific assays to determine nucleotide repeat lengths should be considered first in individuals with hereditary ataxia.
Thursday, March 8, 2018
In the Clinic-Cerebellar Ataxia: How to Treat Cerebellar Ataxia — What the AAN Evidence-Based Guideline Suggests
Samson, Kurt. Neurology Today: March 8, 2018 - Volume 18 - Issue 5 - p 34–36 doi: 10.1097/01.NT.0000531206.29854.dd
A systematic review of studies on cerebellar motor dysfunction and ataxia revealed a dearth of good evidence for therapies. In part, the author panel found that the heterogeneous nature of the disorders that comprise cerebellar ataxia make it difficult to study.
A systematic review of studies on cerebellar motor dysfunction and ataxia revealed a dearth of good evidence for therapies. In part, the author panel found that the heterogeneous nature of the disorders that comprise cerebellar ataxia make it difficult to study.
Channelopathies influence on neurotransmitters monitorable by real time in situ voltammetry, a review and research proposal
Crespi F (2018). Med Clin Arch 2: DOI: 10.15761/MCA.1000128
It has been observed that 5-hydroxytryptophan, serotonin precursor, is more effective than placebo improving neurological symptoms in patients with Friedreich ataxia (FA). FA is an autosomal recessive genetic illness responsible for progressive damage to the nervous system in the spinal cord, in particular of sensory neurons basal for leading muscle motion of the arms and legs via link with the cerebellum.
It has been observed that 5-hydroxytryptophan, serotonin precursor, is more effective than placebo improving neurological symptoms in patients with Friedreich ataxia (FA). FA is an autosomal recessive genetic illness responsible for progressive damage to the nervous system in the spinal cord, in particular of sensory neurons basal for leading muscle motion of the arms and legs via link with the cerebellum.
Iron–sulfur clusters: from metals through mitochondria biogenesis to disease
Cardenas-Rodriguez, M., Chatzi, A. & Tokatlidis, K. J Biol Inorg Chem (2018). doi:10.1007/s00775-018-1548-6
Frataxin is involved in Fe–S clusters biogenesis. Thus, alterations linked to iron metabolism are present in FRDA. The pathophysiology of FRDA comprises deficit of aconitase and respiratory chain complexes, presence of oxidative damage markers in blood and urine, and intracellular iron accumulation [82, 84, 85, 86]. Currently, no successful treatment is available for FRDA. One main reason for this is the lack of understood detailed understanding of mechanisms of Fe–S cluster biogenesis and appropriate disease models.
Frataxin is involved in Fe–S clusters biogenesis. Thus, alterations linked to iron metabolism are present in FRDA. The pathophysiology of FRDA comprises deficit of aconitase and respiratory chain complexes, presence of oxidative damage markers in blood and urine, and intracellular iron accumulation [82, 84, 85, 86]. Currently, no successful treatment is available for FRDA. One main reason for this is the lack of understood detailed understanding of mechanisms of Fe–S cluster biogenesis and appropriate disease models.
Friedreich Ataxia Scientific News: Monthly update: February 7- March 8, 2018
Friedreich Ataxia Scientific News
Monthly update: February 7- March 8, 2018
Thursday, March 8, 2018
Small RNA-seq analysis of
circulating miRNAs to identify phenotypic variability in Friedreich’s ataxia
patients
Friday, March 2, 2018
Neuroimagem na ataxia de Friedreich
= novas abordagens e aplicações clínicas = Neuroimaging in Friedreich's ataxia
= new approaches and clinical aplication
Thursday, March 1, 2018
Tuesday, February 27, 2018
Monday, February 26, 2018
Friday, February 23, 2018
Thursday, February 22, 2018
Wednesday, February 21, 2018
Tuesday, February 20, 2018
Meet Our Scientists. Ernest Giralt:
"There are many diseases caused by failures in the protein-protein
interactions”
Friday, February 16, 2018
Thursday, February 15, 2018
Comprehensive systematic review
summary: Treatment of cerebellar motor dysfunction and ataxia Report of the
Guideline Development, Dissemination, and Implementation Subcommittee of the
American Academy of Neurology
Tuesday, February 13, 2018
Restless
legs syndrome and periodic leg movements in patients with movement disorders:
Specific considerations
Wednesday, February 7, 2018
Small RNA-seq analysis of circulating miRNAs to identify phenotypic variability in Friedreich’s ataxia patients
Marta Seco-Cervera, Dayme González-Rodríguez, José Santiago Ibáñez-Cabellos, Lorena Peiró-Chova, Federico V Pallardó & José Luis García-Giménez; Sci. Data 5:180021 doi: 10.1038/sdata.2018.21 (2018).
Friedreich’s ataxia (FRDA; OMIM 229300), an autosomal recessive neurodegenerative mitochondrial disease, is the most prevalent hereditary ataxia. In addition, FRDA patients have shown additional non-neurological features such as scoliosis, diabetes, and cardiac complications. Hypertrophic cardiomyopathy, which is found in two thirds of patients at the time of diagnosis, is the primary cause of death in these patients. Here, we used small RNA-seq of microRNAs (miRNAs) purified from plasma samples of FRDA patients and controls. Furthermore, we present the rationale, experimental methodology, and analytical procedures for dataset analysis. This dataset will facilitate the identification of miRNA signatures and provide new molecular explanation for pathological mechanisms occurring during the natural history of FRDA. Since miRNA levels change with disease progression and pharmacological interventions, miRNAs will contribute to the design of new therapeutic strategies and will improve clinical decisions.
Friedreich’s ataxia (FRDA; OMIM 229300), an autosomal recessive neurodegenerative mitochondrial disease, is the most prevalent hereditary ataxia. In addition, FRDA patients have shown additional non-neurological features such as scoliosis, diabetes, and cardiac complications. Hypertrophic cardiomyopathy, which is found in two thirds of patients at the time of diagnosis, is the primary cause of death in these patients. Here, we used small RNA-seq of microRNAs (miRNAs) purified from plasma samples of FRDA patients and controls. Furthermore, we present the rationale, experimental methodology, and analytical procedures for dataset analysis. This dataset will facilitate the identification of miRNA signatures and provide new molecular explanation for pathological mechanisms occurring during the natural history of FRDA. Since miRNA levels change with disease progression and pharmacological interventions, miRNAs will contribute to the design of new therapeutic strategies and will improve clinical decisions.
Wednesday, March 7, 2018
Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
Luis Rajman, Karolina Chwalek, David A. Sinclair, Cell Metabolism, Volume 27, Issue 3, 6 March 2018, Pages 529-547, ISSN 1550-4131, doi:10.1016/j.cmet.2018.02.011.
Nicotinamide adenine dinucleotide (NAD), the cell’s hydrogen carrier for redox enzymes, is well known for its role in redox reactions. More recently, it has emerged as a signaling molecule. By modulating NAD+-sensing enzymes, NAD+ controls hundreds of key processes from energy metabolism to cell survival, rising and falling depending on food intake, exercise, and the time of day. NAD+ levels steadily decline with age, resulting in altered metabolism and increased disease susceptibility. Restoration of NAD+ levels in old or diseased animals can promote health and extend lifespan, prompting a search for safe and efficacious NAD-boosting molecules that hold the promise of increasing the body’s resilience, not just to one disease, but to many, thereby extending healthy human lifespan.
Nicotinamide adenine dinucleotide (NAD), the cell’s hydrogen carrier for redox enzymes, is well known for its role in redox reactions. More recently, it has emerged as a signaling molecule. By modulating NAD+-sensing enzymes, NAD+ controls hundreds of key processes from energy metabolism to cell survival, rising and falling depending on food intake, exercise, and the time of day. NAD+ levels steadily decline with age, resulting in altered metabolism and increased disease susceptibility. Restoration of NAD+ levels in old or diseased animals can promote health and extend lifespan, prompting a search for safe and efficacious NAD-boosting molecules that hold the promise of increasing the body’s resilience, not just to one disease, but to many, thereby extending healthy human lifespan.
Friedreich Ataxia: Clinical Report of an Uncommon Point Mutation (R165C)
Rosa María García Tercero*, Javier Gualda Heras, Catalina Diaz Urrea, Pedro Barredo Benitez, Adolfo Heras Pérez, Fátima López González, Blanca serrano Serrano, Elena Elvira Soler and Carmina Díaz Marín; J Neurol Disord 2018, 6:1 DOI:10.4172/2329-6895.1000376
Despite of been inherited as a recessive disease, Friedreich ataxia (FRDA) there is not such clinical homogeneity as in other recessive disorders and due to the atypical presentation of our patient, another sensitives neuropathies were taken into account and a differential diagnosis were made with them (hereditary sensory and autonomic neuropathy, Fabry disease, Familial amyloidotic polyneuropathy, Adrenomyeloneuropathy etc.) but the normality of the probes that have been done and the lack of another symptoms related with these diseases caused that Friedreich ataxia was suspected. With this case we make relevance that not all patients have an early onset, or a severe phenotype and a good neurologic exploration is important to recognize them. Once the diagnosis is made, it is necessary to follow them in consults paying attention to heart problems and giving them genetic counseling.
Despite of been inherited as a recessive disease, Friedreich ataxia (FRDA) there is not such clinical homogeneity as in other recessive disorders and due to the atypical presentation of our patient, another sensitives neuropathies were taken into account and a differential diagnosis were made with them (hereditary sensory and autonomic neuropathy, Fabry disease, Familial amyloidotic polyneuropathy, Adrenomyeloneuropathy etc.) but the normality of the probes that have been done and the lack of another symptoms related with these diseases caused that Friedreich ataxia was suspected. With this case we make relevance that not all patients have an early onset, or a severe phenotype and a good neurologic exploration is important to recognize them. Once the diagnosis is made, it is necessary to follow them in consults paying attention to heart problems and giving them genetic counseling.
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