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ABCD2

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Stephane Savary – 1st expert on this subject based on the ideXlab platform

  • Dehydroepiandrosterone Induction of the ABCD2 and Abcd3 Genes encoding peroxisomal ABC Transporters
    Advances in Experimental Medicine and Biology, 2020
    Co-Authors: Fabien Gueugnon, Stephane Savary, Catherine Gondcaille, Jerome Bellenger, Stephane Fourcade, Francoise Cadepond, Fabrice Lambert, Maurice Bugaut

    Abstract:

    Dehydroepiandrosterone (DHEA) is a peroxisome proliferator known to increase the expression of the genes encoding the peroxisomal s-oxidation enzymes in rodents. Using RT-PCR, we analysed the expression of the ABCD2 and Abcd3 genes encoding the peroxisomal ABC transporters ALDRP (ALD related protein) and PMP70 (70 kDa peroxisomal membrane protein) in primary cultures of rats hepatocytes treated with sulfated DHEA. We observed a time (12-72h) and dose (125-500μM) dependent increase in the expression of both genes.

  • crispr cas9 mediated knockout of abcd1 and ABCD2 genes in bv 2 cells novel microglial models for x linked adrenoleukodystrophy
    Biochimica et Biophysica Acta, 2019
    Co-Authors: Quentin Raas, Catherine Gondcaille, Doriane Trompier, Gerard Lizard, Franck Ménétrier, Yannick Hamon, Valerio Leoni, Claudio Caccia, Stephane Savary

    Abstract:

    X-linked adrenoleukodystrophy (X-ALD), the most frequent peroxisomal disorder, is associated with mutation in the ABCD1 gene which encodes a peroxisomal ATP-binding cassette transporter for very long-chain fatty acids (VLCFA). The biochemical hallmark of the disease is the accumulation of VLCFA. Peroxisomal defect in microglia being now considered a priming event in the pathology, we have therefore generated murine microglial cells mutated in the Abcd1 gene and its closest homolog, the ABCD2 gene. Using CRISPR/Cas9 gene editing strategy, we obtained 3 cell clones with a single or double deficiency. As expected, only the combined absence of ABCD1 and ABCD2 proteins resulted in the accumulation of VLCFA. Ultrastructural analysis by electron microscopy revealed in the double mutant cells the presence of lipid inclusions similar to those observed in brain macrophages of patients. These observations are likely related to the increased level of cholesterol and the accumulation of neutral lipids that we noticed in mutant cells. A preliminary characterization of the impact of peroxisomal defects on the expression of key microglial genes such as Trem2 suggests profound changes in microglial functions related to inflammation and phagocytosis. The expression levels of presumed modifier genes have also been found modified in mutant cells, making these novel cell lines relevant for use as in vitro models to better understand the physiopathogenesis of X-ALD and to discover new therapeutic targets.

  • regulation of the adrenoleukodystrophy related gene ABCD2 focus on oxysterols and lxr antagonists
    Biochemical and Biophysical Research Communications, 2014
    Co-Authors: Doriane Trompier, Catherine Gondcaille, Gerard Lizard, Stephane Savary

    Abstract:

    Abstract The regulation of the ABCD2 gene is recognized as a possible therapeutic target for X-linked adrenoleukodystrophy, a rare neurodegenerative disease caused by mutations in the ABCD1 gene. Up-regulation of ABCD2 expression has indeed been demonstrated to compensate for ABCD1 deficiency, restoring peroxisomal β-oxidation of very-long-chain fatty acids. Besides the known inducers of the ABCD2 gene (phenylbutyrate and histone deacetylase inhibitors, fibrates, dehydroepiandrosterone, thyroid hormone and thyromimetics), this review will focus on LXR antagonists and 22S-hydroxycholesterol, recently described as inducers of ABCD2 expression. Several LXR antagonists have been identified and their possible indication for neurodegenerative disorders will be discussed.

Per Wester – 2nd expert on this subject based on the ideXlab platform

  • Prediction of recurrent stroke with ABCD2 and ABCD3 scores in patients with symptomatic 50-99% carotid stenosis
    BMC Neurology, 2014
    Co-Authors: Elias Johansson, Jakob Bjellerup, Per Wester

    Abstract:

    Although it is preferable that all patients with a recent Transient Ischemic Attack (TIA) undergo acute carotid imaging, there are centers with limited access to such acute examinations. It is controversial whether ABCD2 or ABCD3 scores can be used to triage patients to acute or delayed carotid imaging. It would be acceptable that some patients with a symptomatic carotid stenosis are detected with a slight delay as long as those who will suffer an early recurrent stroke are detected within 24 hours. The aim of this study is to analyze the ability of ABCD2 and ABCD3 scores to predict ipsilateral ischemic stroke among patients with symptomatic 50-99% carotid stenosis. In this secondary analysis of the ANSYSCAP-study, we included 230 consecutive patients with symptomatic 50-99% carotid stenosis. We analyzed the risk of recurrent ipsilateral ischemic stroke before carotid endarterectomy based on each parameter of the ABCD2 and ABCD3 scores separately, and for total ABCD2 and ABCD3 scores. We used Kaplan-Meier analysis. None of the parameters in the ABCD2 or ABCD3 scores could alone predict all 12 of the ipsilateral ischemic strokes that occurred within 2 days of the presenting event, but clinical presentation tended to be a statistically significant risk factor for recurrent ipsilateral ischemic stroke (p = 0.06, log rank test). An ABCD2 score ≥2 and an ABCD3 score ≥4 could predict all 12 of these strokes as well as all 25 ipsilateral ischemic strokes that occurred within 14 days. To use ABCD3 score seems preferable over the ABCD2 score because a higher proportion of low risk patients were identified (17% of the patients had an ABCD3 score

  • prediction of recurrent stroke with ABCD2 and abcd3 scores in patients with symptomatic 50 99 carotid stenosis
    BMC Neurology, 2014
    Co-Authors: Elias Johansson, Jakob Bjellerup, Per Wester

    Abstract:

    Although it is preferable that all patients with a recent Transient Ischemic Attack (TIA) undergo acute carotid imaging, there are centers with limited access to such acute examinations. It is controversial whether ABCD2 or ABCD3 scores can be used to triage patients to acute or delayed carotid imaging. It would be acceptable that some patients with a symptomatic carotid stenosis are detected with a slight delay as long as those who will suffer an early recurrent stroke are detected within 24 hours. The aim of this study is to analyze the ability of ABCD2 and ABCD3 scores to predict ipsilateral ischemic stroke among patients with symptomatic 50-99% carotid stenosis. In this secondary analysis of the ANSYSCAP-study, we included 230 consecutive patients with symptomatic 50-99% carotid stenosis. We analyzed the risk of recurrent ipsilateral ischemic stroke before carotid endarterectomy based on each parameter of the ABCD2 and ABCD3 scores separately, and for total ABCD2 and ABCD3 scores. We used Kaplan-Meier analysis. None of the parameters in the ABCD2 or ABCD3 scores could alone predict all 12 of the ipsilateral ischemic strokes that occurred within 2 days of the presenting event, but clinical presentation tended to be a statistically significant risk factor for recurrent ipsilateral ischemic stroke (p = 0.06, log rank test). An ABCD2 score ≥2 and an ABCD3 score ≥4 could predict all 12 of these strokes as well as all 25 ipsilateral ischemic strokes that occurred within 14 days. To use ABCD3 score seems preferable over the ABCD2 score because a higher proportion of low risk patients were identified (17% of the patients had an ABCD3 score <4 while only 6% had an ABCD2 < 2). Although it is preferable that carotid imaging be performed within 24 hours, our data support that an ABCD3 score ≥4 might be used for triaging patients to acute carotid imaging in clinical settings with limited access to carotid imaging. However, our findings should be validated in a larger cohort study.

Borislav D Dimitrov – 3rd expert on this subject based on the ideXlab platform

  • long term risk of stroke after transient ischaemic attack a hospital based validation of the ABCD2 rule
    BMC Research Notes, 2014
    Co-Authors: Rose Galvin, Borislav D Dimitrov, Penka A Atanassova, Nicola Motterlini, Tom Fahey

    Abstract:

    Background
    The ABCD2 clinical prediction rule is a seven point summation of clinical factors independently predictive of stroke risk. The purpose of this cohort study is to validate the ABCD2 rule in a Bulgarian hospital up to three years after TIA.