This service exclusively searches for literature that cites resources. Please be aware that the total number of searchable documents is limited to those containing RRIDs and does not include all open-access literature.
Currently the molecular basis for the clinical heterogeneity of X-linked adrenoleukodystrophy (X-ALD) is poorly understood. The genetic bases for all different phenotypic variants of X-ALD are mutations in the gene encoding the peroxisomal ATP-binding cassette (ABC) transporter, ABCD1 (formerly adrenoleukodystrophy protein, ALDP). ABCD1 transports CoA-activated very long-chain fatty acids from the cytosol into the peroxisome for degradation. The phenotypic variability is remarkable ranging from cerebral inflammatory demyelination of childhood onset, leading to death within a few years, to adults remaining pre-symptomatic through more than five decades. There is no general genotype-phenotype correlation in X-ALD. The default manifestation of mutations in ABCD1 is adrenomyeloneuropathy, a slowly progressive dying-back axonopathy affecting both ascending and descending spinal cord tracts as well as in some cases, a peripheral neuropathy. In about 60% of male X-ALD patients, either in childhood (35-40%) or in adulthood (20%), an initial, clinically silent, myelin destabilization results in conversion to a devastating, rapidly progressive form of cerebral inflammatory demyelination. Here, ABCD1 remains a susceptibility gene, necessary but not sufficient for inflammatory demyelination to occur. Although the accumulation of very long-chain fatty acids appears to be essential for the pathomechanism of all phenotypes, the molecular mechanisms underlying these phenotypes are fundamentally different. Cell autonomous processes such as oxidative stress and energy shortage in axons as well as non-cell autonomous processes involving axon-glial interactions seem pertinent to the dying-back axonopathy. Various dynamic mechanisms may underlie the initiation of inflammation, the altered immune reactivity, the propagation of inflammation, as well as the mechanisms leading to the arrest of inflammation after hematopoietic stem cell transplantation. An improved understanding of the molecular mechanisms involved in these events is required for the development of urgently needed therapeutics.
X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene and is characterized by impaired beta-oxidation of very-long-chain fatty acids (VLCFA) and subsequent VLCFA accumulation in tissues. In adulthood X-ALD most commonly manifests as a gradually progressive myelopathy, (adrenomyeloneuropathy; AMN) without any curative or disease modifying treatments. We recently showed that bezafibrate (BF), a drug used for the treatment of hyperlipidaemia, reduces VLCFA accumulation in X-ALD fibroblasts by inhibiting ELOVL1, an enzyme involved in the VLCFA synthesis. We therefore designed a proof-of-principal clinical trial to determine whether BF reduces VLCFA levels in plasma and lymphocytes of X-ALD patients. Ten males with AMN were treated with BF for 12 weeks at a dose of 400 mg daily, followed by 12 weeks of 800 mg daily. Every 4 weeks patients were evaluated for side effects and blood samples were taken for analysis. Adherence was good as indicated by a clear reduction in triglycerides. There was no reduction in VLCFA in either plasma or lymphocytes. Plasma levels of BF did not exceed 25 µmol/L. We concluded that BF, at least in the dose given, is unable to lower VLCFA levels in plasma or lymphocytes in X-ALD patients. It is unclear whether this is due to the low levels of BF reached in plasma. Our future work is aimed at the identification of highly-specific inhibitors of ELOVL1 that act at much lower concentrations than BF and are well tolerated. BF appears to have no therapeutic utility in X-ALD.
Precise pathophysiology with respect to the phenotypic variations and severity of X-ALD, specifically between adrenomyeloneuropathy (AMN) and childhood cerebral adrenoleukodystrophy (CCALD), has not been fully discovered. Herein, a systematic analysis using multi-layered lipidomics and transcriptomics was conducted to elucidate distinctive metabolic biosignatures among healthy control, AMN, and CCALD. Significant alterations regarding the accumulation of very long chain fatty acids were found in various lipid species such as phospholipids, glycerolipids, and sphingolipids. Remarkably, TG and CER that are physiologically essential were markedly down-regulated in CCALD than AMN. Transcriptomic analysis further supported the robustness of our findings by providing valuable information on the gene expressions of the regulatory factors. For instance, regulators of sphingolipid catabolism (SMPD1, CERK, and SPHK1) and TG anabolism (GPAM, GPAT2, and MBOAT2) were more up-regulated in AMN than in CCALD. These observations, among others, were in line with the recognized alterations of the associated lipidomes. In conclusion, the homeostatic imbalance of the complex lipid networks may be pathogenically important in X-ALD and the particular dysregulations of TG and CER may further influence the severity of CCALD among X-ALD patients.
X-linked adrenoleukodystrophy (X-ALD) is a clinically heterogeneous disorder ranging from the severe childhood cerebral form to asymptomatic persons. The overall incidence is 1:16,800 including hemizygotes as well as heterozygotes. The principal molecular defect is due to inborn mutations in the ABCD1 gene encoding the adrenoleukodystrophy protein (ALDP), a transporter in the peroxisome membrane. ALDP is involved in the transport of substrates from the cytoplasm into the peroxisomal lumen. ALDP defects lead to characteristic accumulation of saturated very long-chain fatty acids, the diagnostic disease marker. The pathogenesis is unclear. Different molecular mechanisms seem to induce inflammatory demyelination, neurodegeneration and adrenocortical insufficiency involving the primary ABCD1 defect, environmental factors and modifier genes. Important information has been derived from the X-ALD mouse models; species differences however complicate the interpretation of results. So far, bone marrow transplantation is the only effective long-term treatment for childhood cerebral X-ALD, however, only when performed at an early-stage of disease. Urgently needed novel therapeutic strategies are under consideration ranging from dietary approaches to gene therapy.
Adrenoleukodystrophy (ALD) is a rare and progressive neurogenetic disease that may manifest disparate symptoms. The present study aims at investigating the role of ataxic variant of ALD (AVALD) in patients with adult-onset cerebellar ataxia, as well as characterizing their clinical features that distinguish AVALD from other cerebellar ataxias. Mutations in the ATP binding cassette subfamily D member 1 gene (ABCD1) were ascertained in 516 unrelated patients with ataxia. The patients were categorized into three groups: molecularly unassigned hereditary ataxia (n = 118), sporadic ataxia with autonomic dysfunctions (n = 296), and sporadic ataxia without autonomic dysfunctions (n = 102). Brain MRIs were scrutinized for white matter hyperintensity (WMH) in the parieto-occipital lobes, frontal lobes, corticospinal tracts, pons, middle cerebellar peduncles and cerebellar hemispheres. Two ABCD1 mutations (p.S108L and p.P623fs) previously linked to cerebral ALD and adrenomyeloneuropathy but not AVALD were identified. ALD accounts for 0.85% (1/118) of the patients with molecularly unassigned hereditary ataxia and 0.34% (1/296) of the patients with sporadic ataxia with autonomic dysfunctions. WMH in the corticospinal tracts and WMH in the cerebellar hemispheres were strongly associated with AVALD rather than other ataxias. To conclude, ALD accounts for approximately 0.39% (2/516) of adult-onset cerebellar ataxias. This study expands the mutational spectrum of AVALD and underscores the importance of considering ALD as a potential etiology of cerebellar ataxia.
Epigenomic changes may either cause disease or modulate its expressivity, adding a layer of complexity to mendelian diseases. X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic condition exhibiting discordant phenotypes, ranging from a childhood cerebral inflammatory demyelination (cALD) to an adult-onset mild axonopathy in spinal cords (AMN). The AMN form may occur with superimposed inflammatory brain demyelination (cAMN). All patients harbor loss of function mutations in the ABCD1 peroxisomal transporter of very-long chain fatty acids. The factors that account for the lack of genotype-phenotype correlation, even within the same family, remain largely unknown. To gain insight into this matter, here we compared the genome-wide DNA methylation profiles of morphologically intact frontal white matter areas of children affected by cALD with adult cAMN patients, including male controls in the same age group. We identified a common methylomic signature between the two phenotypes, comprising (i) hypermethylation of genes harboring the H3K27me3 mark at promoter regions, (ii) hypermethylation of genes with major roles in oligodendrocyte differentiation such as MBP, CNP, MOG and PLP1 and (iii) hypomethylation of immune-associated genes such as IFITM1 and CD59. Moreover, we found increased hypermethylation in CpGs of genes involved in oligodendrocyte differentiation, and also in genes with H3K27me3 marks in their promoter regions in cALD compared with cAMN, correlating with transcriptional and translational changes. Further, using a penalized logistic regression model, we identified the combined methylation levels of SPG20, UNC45A and COL9A3 and also, the combined expression levels of ID4 and MYRF to be good markers capable of discriminating childhood from adult inflammatory phenotypes. We thus propose the hypothesis that an epigenetically controlled, altered transcriptional program may drive an impaired oligodendrocyte differentiation and aberrant immune activation in X-ALD patients. These results shed light into disease pathomechanisms and uncover putative biomarkers of interest for prognosis and phenotypic stratification.
Males with X-linked adrenoleukodystrophy (ALD) are at high risk for developing adrenal insufficiency and/or progressive leukodystrophy (cerebral ALD) at an early age. Pathogenic variants in ABCD1 result in elevated levels of very long-chain fatty acids (VLCFA), including C26:0-lysophosphatidylcholine (C26:0-LPC). Newborn screening for ALD enables prospective monitoring and timely therapeutic intervention, thereby preventing irreversible damage and saving lives. The Dutch Health Council recommended to screen only male newborns for ALD without identifying untreatable conditions associated with elevated C26:0-LPC, like Zellweger spectrum disorders and single peroxisomal enzyme defects. Here, we present the results of the SCAN (Screening for ALD in the Netherlands) study which is the first sex-specific newborn screening program worldwide. Males with ALD are identified based on elevated C26:0-LPC levels, the presence of one X-chromosome and a variant in ABCD1, in heel prick dried bloodspots. Screening of 71 208 newborns resulted in the identification of four boys with ALD who, following referral to the pediatric neurologist and confirmation of the diagnosis, enrolled in a long-term follow-up program. The results of this pilot show the feasibility of employing a boys-only screening algorithm that identifies males with ALD without identifying untreatable conditions. This approach will be of interest to countries that are considering ALD newborn screening but are reluctant to identify girls with ALD because for girls there is no direct health benefit. We also analyzed whether gestational age, sex, birth weight and age at heel prick blood sampling affect C26:0-LPC concentrations and demonstrate that these covariates have a minimal effect.
X-linked adrenoleukodystrophy is caused by ATP-binding cassette transporter D1 (ABCD1) mutations and manifests by default as slowly progressive spinal cord axonopathy with associated demyelination (adrenomyloneuropathy). In 60% of male cases, however, X-linked adrenoleukodystrophy converts to devastating cerebral inflammation and demyelination (cerebral adrenoleukodystrophy) with infiltrating blood-derived monocytes and macrophages and cytotoxic T cells that can only be stopped by allogeneic haematopoietic stem cell transplantation or gene therapy at an early stage of the disease. Recently, we identified monocytes/macrophages but not T cells to be severely affected metabolically by ABCD1 deficiency. Here we found by whole transcriptome analysis that, although monocytes of patients with X-linked adrenoleukodystrophy have normal capacity for macrophage differentiation and phagocytosis, they are pro-inflammatory skewed also in patients with adrenomyloneuropathy in the absence of cerebral inflammation. Following lipopolysaccharide activation, the ingestion of myelin debris, normally triggering anti-inflammatory polarization, did not fully reverse the pro-inflammatory status of X-linked adrenoleukodystrophy macrophages. Immunohistochemistry on post-mortem cerebral adrenoleukodystrophy lesions reflected the activation pattern by prominent presence of enlarged lipid-laden macrophages strongly positive for the pro-inflammatory marker co-stimulatory molecule CD86. Comparative analyses of lesions with matching macrophage density in cases of cerebral adrenoleukodystrophy and acute multiple sclerosis showed a similar extent of pro-inflammatory activation but a striking reduction of anti-inflammatory mannose receptor (CD206) and haemoglobin-haptoglobin receptor (CD163) expression on cerebral adrenoleukodystrophy macrophages. Accordingly, ABCD1-deficiency leads to an impaired plasticity of macrophages that is reflected in incomplete establishment of anti-inflammatory responses, thus possibly contributing to the devastating rapidly progressive demyelination in cerebral adrenoleukodystrophy that only in rare cases arrests spontaneously. These findings emphasize monocytes/macrophages as crucial therapeutic targets for preventing or stopping myelin destruction in patients with X-linked adrenoleukodystrophy.
X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease resulting from mutations in the gene ABCD1 and alterations in peroxisomal beta-oxidation of long chain fatty acids. As it has been frequently discussed, it manifests a wide range of phenotypes in male, with progressive myelopathy being the most common. Even though the gene is localized to the X-chromosome and a region subject to X-inactivation, female carriers still are affected significantly by this condition. It has been stated that between 20 and 50% of women who are carriers may manifest some symptoms and recent evidence has suggested the differences in disease manifestations and relative rates of progression between men and women. However there have been only limited studies specifically addressing this and to date there has been no comprehensive review discussing the different phenotypes in female carriers, as well as the differences in disease onset, progression, disability, nervous system pathology and neuroimaging patterns compared to affected males. This is of key importance as similarities and differences between genders will assist in determining how best to target therapies in all affected individuals as opportunities for treatment present themselves. As will be further addressed in this review, we need to improve our understanding of the associations of emergent neuroimaging techniques to physical disability in this population. We reviewed the clinical presentations in the carrier population, the distinct disability profile and neuroimaging findings in order to put together pieces of this neglected segment in X-ALD and give direction to further studies.
X-linked adrenoleukodystrophy (X-ALD) is a progressive peroxisomal disorder affecting adrenal glands, testes and myelin stability that is caused by mutations in the ABCD1 (NM_000033) gene. Males with X-ALD may be diagnosed by the demonstration of elevated very long chain fatty acid (VLCFA) levels in plasma. In contrast, only 80% of female carriers have elevated plasma VLCFA; therefore targeted mutation analysis is the most effective means for carrier detection. Amongst 489 X-ALD families tested at Kennedy Krieger Institute, we identified 20 cases in which the ABCD1 mutation was de novo in the index case, indicating that the mutation arose in the maternal germ line and supporting a new mutation rate of at least 4.1% for this group. In addition, we identified 10 cases in which a de novo mutation arose in the mother or the grandmother of the index case. In two of these cases studies indicated that the mothers were low level gonosomal mosaics. In a third case biochemical, molecular and pedigree analysis indicated the mother was a gonadal mosaic. To the best of our knowledge mosaicism has not been previously reported in X-ALD. In addition, we identified one pedigree in which the maternal grandfather was mosaic for the familial ABCD1 mutation. Less than 1% of our patient population had evidence of gonadal or gonosomal mosaicism, suggesting it is a rare occurrence for this gene and its associated disorders. However, the residual maternal risk for having additional ovum carrying the mutant allele identified in an index case that appears to have a de novo mutation is at least 13%.
X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder of X-linked inheritance caused by a mutation in the ABCD1 gene which determines an accumulation of long-chain fatty acids in plasma and tissues. Recent evidence shows that oxidative stress may be a hallmark in the pathogenesis of X-ALD and glutathione plays an important role in the defense against free radicals. In this study we have analyzed glutathione homeostasis in lymphocytes of 14 patients with X-ALD and evaluated the balance between oxidized and reduced forms of glutathione, in order to define the role of this crucial redox marker in this condition.
Cerebral adrenoleukodystrophy (cALD) is an inflammatory neurodegenerative disease associated with mutation of the ABCD1 gene. Proteomic analysis of cerebral spinal fluid (CSF) from young males with active cALD revealed markers of inflammation including APOE4. APOE4 genotype has been associated with an inferior prognosis following acute and chronic neurologic injury. We assessed APOE4 inheritance among 83 consecutive young males with cALD prior to hematopoietic cell transplant and its association with markers of cerebral disease. The allele frequency of APOE4 was not significantly different from that of the general population at 17%. Young males with cALD that were APOE4 carriers had similar CSF protein and chitotriosidase activity to that of non-carriers. In contrast, APOE4 carriers had an increased burden of cerebral disease involvement as determined by MRI severity score (10.5 vs 7.0 points, p = 0.01), higher gadolinium intensity score (2.0 vs 1.3 points, p = 0.007), inferior neurologic function (neurologic function score 2.4 vs 1.0, p = 0.001), and elevated CSF MMP2 levels compared to that of non-carriers (13168 vs 9472 pg/mL, p = 0.01). These are the first data showing that APOE4 is associated with increased severity of cerebral disease in cALD and suggest it may be a modifier of disease.
X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease. The two main clinical phenotypes of X-ALD are adrenomyeloneuropathy (AMN) and inflammatory cerebral ALD that manifests either in children or more rarely in adults. About 65% of heterozygote females develop symptoms by the age of 60years. Mutations in the ABCD1 gene affect the function of the encoded protein ALDP, an ATP-binding-cassette (ABC) transporter located in the peroxisomal membrane protein. ALDP deficiency impairs the peroxisomal beta-oxidation of very long-chain fatty acids (VLCFA) and facilitates their further chain elongation by ELOVL1 resulting in accumulation of VLCFA in plasma and tissues. While all patients have mutations in the ABCD1 gene, there is no general genotype-phenotype correlation. Environmental factors and a multitude of modifying genes appear to determine the clinical manifestation in this monogenetic but multifactorial disease. This review focuses on the clinical, biochemical, genetic and pathophysiological aspects of X-ALD.
Redox imbalance, mitochondrial dysfunction, and inflammation play a major role in the pathophysiology of X-linked adrenoleukodystrophy (X-ALD), an inherited neurodegenerative disease caused by mutations in the ABCD1 gene, encoding the protein responsible for peroxisomal import and degradation of very long chain fatty acids (VLCFAs). Therefore, VLCFAs accumulate in tissues and plasma, constituting a pathognomonic biomarker for diagnosis. However, the precise role of VLCFA accumulation on the diverse clinical phenotypes of X-ALD and the pathogenic link between VLCFAs and oxidative stress remain currently unclear. This study proposes ferroptosis as a crucial contributor to the disease development and progression. The expression profiles of "GPX4-glutathione" and "NQO1-CoQ10" ferroptosis pathways have been analyzed in fibroblasts of one patient with AMN, the late onset and slowly progressive form of X-ALD, and in two patients with cALD, the cerebral inflammatory demyelinating form of early childhood. Furthermore, as no effective treatments are currently available, especially for the rapidly progressing form of X-ALD (cALD), the efficacy of NAC treatment has also been evaluated to open the way toward novel combined therapies. Our findings demonstrate that lipid peroxides accumulate in X-ALD fibroblasts and ferroptosis-counteracting enzymes are dysregulated, highlighting a different antioxidant response in patients with AMN and cALD.
X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) and (iii) a childhood variant, cALD, characterized by severe cerebral demyelination. Loss of function of the ABCD1 peroxisomal fatty acid transporter and subsequent accumulation of very-long-chain fatty acids (VLCFAs) are the common culprits to all forms of X-ALD, an aberrant microglial activation accounts for the cerebral forms, whereas inflammation allegedly plays no role in AMN. How VLCFA accumulation leads to neurodegeneration and what factors account for the dissimilar clinical outcomes and prognosis of X-ALD variants remain elusive. To gain insights into these questions, we undertook a transcriptomic approach followed by a functional-enrichment analysis in spinal cords of the animal model of AMN, the Abcd1(-) null mice, and in normal-appearing white matter of cAMN and cALD patients. We report that the mouse model shares with cAMN and cALD a common signature comprising dysregulation of oxidative phosphorylation, adipocytokine and insulin signaling pathways, and protein synthesis. Functional validation by quantitative polymerase chain reaction, western blots and assays in spinal cord organotypic cultures confirmed the interplay of these pathways through IkB kinase, being VLCFA in excess a causal, upstream trigger promoting the altered signature. We conclude that X-ALD is, in all its variants, a metabolic/inflammatory syndrome, which may offer new targets in X-ALD therapeutics.
Over 80% of women with X-linked adrenoleukodystrophy (ALD) develop spinal cord disease in adulthood for which treatment is supportive only. For future clinical trials quantitative data on disease progression rates are essential. Moreover, diagnosis can be challenging in ALD women, as the most important diagnostic biomarker is normal in 15-20%. Better biomarkers are needed. The purpose of this single centre cross-sectional follow-up study in women with ALD was to assess whether Expanded Disability Status Scale (EDSS), AMC Linear Disability Scale (ALDS) and Short Form (36) Health Survey (SF-36) can detect disease progression and to model the effect of age and duration of symptoms on the rate of progression. Moreover, we performed a pilot study to assess if a semi-targeted lipidomics approach can identify possible new diagnostic biomarkers.
Accumulated experience supports the efficacy of allogenic haematopoietic stem cell transplantation in arresting the progression of childhood-onset cerebral form of adrenoleukodystrophy in early stages. For adulthood-onset cerebral form of adrenoleukodystrophy, however, there have been only a few reports on haematopoietic stem cell transplantation and the clinical efficacy and safety of that for adulthood-onset cerebral form of adrenoleukodystrophy remain to be established. To evaluate the clinical efficacy and safety of haematopoietic stem cell transplantation, we conducted haematopoietic stem cell transplantation on 12 patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy in a single-institution-based prospective study. Through careful prospective follow-up of 45 male adrenoleukodystrophy patients, we aimed to enrol patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy at early stages. Indications for haematopoietic stem cell transplantation included cerebral form of adrenoleukodystrophy or cerebello-brainstem form of adrenoleukodystrophy with Loes scores up to 13, the presence of progressively enlarging white matter lesions and/or lesions with gadolinium enhancement on brain MRI. Clinical outcomes of haematopoietic stem cell transplantation were evaluated by the survival rate as well as by serial evaluation of clinical rating scale scores and neurological and MRI findings. Clinical courses of eight patients who did not undergo haematopoietic stem cell transplantation were also evaluated for comparison of the survival rate. All the patients who underwent haematopoietic stem cell transplantation survived to date with a median follow-up period of 28.6 months (4.2-125.3 months) without fatality. Neurological findings attributable to cerebral/cerebellar/brainstem lesions became stable or partially improved in all the patients. Gadolinium-enhanced brain lesions disappeared or became obscure within 3.5 months and the white matter lesions of MRI became stable or small. The median Loes scores before haematopoietic stem cell transplantation and at the last follow-up visit were 6.0 and 5.25, respectively. Of the eight patients who did not undergo haematopoietic stem cell transplantation, six patients died 69.1 months (median period; range 16.0-104.1 months) after the onset of the cerebral/cerebellar/brainstem lesions, confirming that the survival probability was significantly higher in patients with haematopoietic stem cell transplantation compared with that in patients without haematopoietic stem cell transplantation (P = 0.0089). The present study showed that haematopoietic stem cell transplantation was conducted safely and arrested the inflammatory demyelination in all the patients with adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy when haematopoietic stem cell transplantation was conducted in the early stages. Further studies are warranted to optimize the procedures of haematopoietic stem cell transplantation for adolescent-/adult-onset cerebral form/cerebello-brainstem form of adrenoleukodystrophy.
X-linked adrenoleukodystrophy (ALD) is a progressive neurodegenerative disease that is caused by mutations in the ABCD1 gene and characterized by elevated levels of very long-chain fatty acids (VLCFA) in plasma and tissues, with the most pronounced increase in the central nervous system. Virtually all male patients develop adrenal insufficiency and myelopathy (adrenomyeloneuropathy), but a subset develops a fatal cerebral demyelinating disease (known as cerebral ALD). Female patients may also develop myelopathy, but adrenal insufficiency or leukodystrophy are very rare. ALD has been associated with mitochondrial dysfunction, oxidative stress and bioenergetic failure, but the mechanism by which VLCFA accumulation triggers these effects has not been resolved thus far. In this study, we used primary human fibroblasts from normal subjects and ALD patients to investigate whether VLCFA can induce endoplasmic reticulum stress. We show that saturated VLCFA (C26:0) induce endoplasmic reticulum stress in fibroblasts from ALD patients, but not in controls. Furthermore, there is a clear correlation between the chain-length of the fatty acid and the induction of endoplasmic reticulum stress. Exposure of ALD fibroblasts to C26:0, resulted in increased expression of additional endoplasmic reticulum stress markers (EDEM1, GADD34 and CHOP) and in lipoapoptosis. This new insight into the underlying mechanism of VLCFA-induced toxicity is of great importance for the development of a disease modifying treatment for ALD aimed at the normalization of VLCFA levels in tissues.
Welcome to the FDI Lab - SciCrunch.org Resources search. From here you can search through a compilation of resources used by FDI Lab - SciCrunch.org and see how data is organized within our community.
You are currently on the Community Resources tab looking through categories and sources that FDI Lab - SciCrunch.org has compiled. You can navigate through those categories from here or change to a different tab to execute your search through. Each tab gives a different perspective on data.
If you have an account on FDI Lab - SciCrunch.org then you can log in from here to get additional features in FDI Lab - SciCrunch.org such as Collections, Saved Searches, and managing Resources.
Here is the search term that is being executed, you can type in anything you want to search for. Some tips to help searching:
You can save any searches you perform for quick access to later from here.
We recognized your search term and included synonyms and inferred terms along side your term to help get the data you are looking for.
If you are logged into FDI Lab - SciCrunch.org you can add data records to your collections to create custom spreadsheets across multiple sources of data.
Here are the facets that you can filter your papers by.
From here we'll present any options for the literature, such as exporting your current results.
If you have any further questions please check out our FAQs Page to ask questions and see our tutorials. Click this button to view this tutorial again.
Year:
Count: