Fungal infection in neural tissue from amyotrophic lateral sclerosis.
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ABSTRACT:
PROVIDER: EGAC00001000664 | EGA |
REPOSITORIES: EGA
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Project description:The study shows that fungus infection, isolated from neural tissue, can be a risk factor to develop Amyothophic lateral sclerosis (ALS).
| EGAS00001002473 | EGA
Project description:Data Access Committee EGAC00001001058
| EGAC00001001058 | EGA
Project description:Despite great efforts in the investigation, the exact etiology of amyotrophic lateral sclerosis (ALS) is a matter of intensive research. We recently advanced the idea that ALS might be caused by fungal infection. Indeed, fungal yeast and hyphal structures can be directly visualized in neural tissue of ALS patients, and a number of fungal species have been identified in the central nervous system (CNS). In the present work, we tested the possibility that bacterial infections can accompany these mycoses. Our findings establish the presence of bacterial DNA in different regions of the CNS from all ALS patients examined. Specifically, we used PCR and next generation sequencing (NGS) to precisely determine the bacterial species present in ALS tissue. Consistent with these findings, immunohistochemistry analysis of CNS sections using specific anti-bacterial antibodies identified prokaryotic cells in neural tissue. Finally, we assayed for the repeat expansion of the hexanucleotide repeat GGGGCC in C9orf72, which is considered the most common genetic cause of ALS in patients, using DNA extracted from ALS CNS tissue. We failed to find this repeated sequence in any of the eleven patients analyzed. Our results indicate that bacterial DNA and prokaryotic cells are present in CNS tissue, leading to the concept that both fungal and bacterial infections coexist in patients with ALS. These observations lay the groundwork for the use of appropriate therapies to eradicate the polymicrobial infections in ALS.
| S-EPMC6399391 | biostudies-literature
Project description:Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients.
| S-EPMC4400386 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE39642: NanoString nCounter immune-related gene expression in blood sorted CD14+CD16- monocytes from sALS, fALS and HC subjects GSE39643: NanoString miRNA profiling of peripheral blood sorted CD14+CD16- monocytes from amyotrophic lateral sclerosis, multiple sclerosis and healthy control subjects Refer to individual Series
2012-07-25 | E-GEOD-39644 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2012-07-26 | GSE39644 | GEO
Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls. Keywords: other
2003-11-14 | GSE833 | GEO
Project description:The study aims to find bacteria in neural tissue from patients with amyotrophic lateral sclerosis
| EGAS00001003295 | EGA
Project description:amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to death within a few years after diagnosis. Malnutrition and weight loss are frequent and are indexes of poor prognosis. Total body fat and fat distribution have not been studied in ALS patients.Our aim was to describe adipose tissue content and distribution in ALS patients.We performed a cross-sectional study in a group of ALS patients (n?=?62, mean disease duration 22 months) along with age and gender matched healthy controls (n?=?62) using a MRI-based method to study quantitatively the fat distribution.Total body fat of ALS patients was not changed as compared with controls. However, ALS patients displayed increased visceral fat and an increased ratio of visceral to subcutaneous fat. Visceral fat was not correlated with clinical severity as judged using the ALS functional rating scale (ALS-FRS-R), while subcutaneous fat in ALS patients correlated positively with ALS-FRS-R and disease progression. Multiple regression analysis showed that gender and ALS-FRS-R, but not site of onset, were significant predictors of total and subcutaneous fat. Increased subcutaneous fat predicted survival in male patients but not in female patients (p<0.05).Fat distribution is altered in ALS patients, with increased visceral fat as compared with healthy controls. Subcutaneous fat content is a predictor of survival of ALS patients.
| S-EPMC3694869 | biostudies-other
Project description:Amyotrophic lateral sclerosis is a fatal CNS neurodegenerative disease. Despite intensive research, current management of amyotrophic lateral sclerosis remains suboptimal from diagnosis to prognosis. Recognition of the phenotypic heterogeneity of amyotrophic lateral sclerosis, global CNS dysfunction, genetic architecture, and development of novel diagnostic criteria is clarifying the spectrum of clinical presentation and facilitating diagnosis. Insights into the pathophysiology of amyotrophic lateral sclerosis, identification of disease biomarkers and modifiable risks, along with new predictive models, scales, and scoring systems, and a clinical trial pipeline of mechanism-based therapies, are changing the prognostic landscape. Although most recent advances have yet to translate into patient benefit, the idea of amyotrophic lateral sclerosis as a complex syndrome is already having tangible effects in the clinic. This Seminar will outline these insights and discuss the status of the management of amyotrophic lateral sclerosis for the general neurologist, along with future prospects that could improve care and outcomes for patients with amyotrophic lateral sclerosis.
| S-EPMC10089700 | biostudies-literature