Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of amyotrophic lateral sclerosis (ALS) and cerebral glioblastoma multiforme is presented in which bizarre astrocytes were found in the degenerating lateral corticospinal tracts, along with Rosenthal fibers, which were present in the corticospinal tracts of the lower medulla and spinal cord, and in anterior horns. These bizarre astrocytes did not result from direct infiltration of tumor from the cerebrum. "Malignant transformation" and/or an exceptionally intense glial response to the corticospinal tract degeneration are discussed as possibilities for the development of these bizarre astrocytes. Rosenthal fiber formation is described, to our knowledge, for the first time in ALS.
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PMID:Atypical astrocytes and Rosenthal fibers in a case of amyotrophic lateral sclerosis associated with a cerebral glioblastoma multiforme. 16 57

In 1983, reports of antibodies in subjects with major depressive disorder (MDD) to an as-yet uncharacterized infectious agent associated with meningoencephalitis in horses and sheep led to molecular cloning of the genome of a novel, negative-stranded neurotropic virus, Borna disease virus (BDV). This advance has enabled the development of new diagnostic assays, including in situ hybridization, PCR and serology based on recombinant proteins. Since these assays were first implemented in 1990, more than 80 studies have reported an association between BDV and a wide range of human illnesses that include MDD, bipolar disorder (BD), schizophrenia (SZ), anxiety disorder, chronic fatigue syndrome, multiple sclerosis, amyotrophic lateral sclerosis, dementia and glioblastoma multiforme. However, to date there has been no blinded case-control study of the epidemiology of BDV infection. Here, in a United States-based, multi-center, yoked case-control study with standardized methods for clinical assessment and blinded serological and molecular analysis, we report the absence of association of psychiatric illness with antibodies to BDV or with BDV nucleic acids in serially collected serum and white blood cell samples from 396 subjects, a study population comprised of 198 matched pairs of patients and healthy controls (52 SZ/control pairs, 66 BD/control pairs and 80 MDD/control pairs). Our results argue strongly against a role for BDV in the pathogenesis of these psychiatric disorders.
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PMID:Absence of evidence for bornavirus infection in schizophrenia, bipolar disorder and major depressive disorder. 2231 May 59

Advanced grades of glioblastoma are highly aggressive, especially in terms of multisite spread within the brain or even to distant sites at the spinal cord. In advanced grades of glioblastoma, glutamate and glutamine are reported to be increased in concentration in the extracellular fluid. It has been reported that glutamate acts as an extracellular signaling molecule for facilitating local spread of advanced grades of glioblastoma. In the present study, we aimed to examine whether glutamate uptake mechanisms is impaired in advanced glioblastoma. The possible downregulated mechanisms of glutamate uptake would facilitate persistence of glutamate in the extracellular environment, rather than intracellular uptake. We obtained biobanked human specimens of glioblastoma and tested expression of proteins belonging to the solute carrier families of proteins that are known to function as membrane-located excitatory amino acid like glutamate transporters. The present study provides preliminary evidence of the downregulation of membrane expression of excitatory amino acid transporters solute carrier family 1 member 3 (SLC1A3) and its palmitoylated form in gliosomes, as well as SLC1A2 in the glio-synaptosomes. Compounds like riluzole used in the treatment of amyotrophic lateral sclerosis and the antibiotic ceftriaxone have the potential to facilitate glutamate uptake. These medications may be examined as adjunct chemotherapy in the massively aggressive tumor glioblastoma multiforme.
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PMID:Downregulation of solute carriers of glutamate in gliosomes and synaptosomes may explain local brain metastasis in anaplastic glioblastoma. 2591 26

Living cells experience DNA damage as a result of replication errors and oxidative metabolism, exposure to environmental agents (e.g., ultraviolet light, ionizing radiation (IR)), and radiation therapies and chemotherapies for cancer treatments. Accumulation of DNA damage can lead to multiple diseases such as neurodegenerative disorders, cancers, immune deficiencies, infertility, and also aging. Cells have evolved elaborate mechanisms to deal with DNA damage. Networks of DNA damage response (DDR) pathways are coordinated to detect and repair DNA damage, regulate cell cycle and transcription, and determine the cell fate. Upstream factors of DNA damage checkpoints and repair, "sensor" proteins, detect DNA damage and send the signals to downstream factors in order to maintain genomic integrity. Unexpectedly, we have discovered that an RNA-processing factor is involved in DNA repair processes. We have identified a gene that contributes to glioblastoma multiforme (GBM)'s treatment resistance and recurrence. This gene, RBM14, is known to function in transcription and RNA splicing. RBM14 is also required for maintaining the stem-like state of GBM spheres, and it controls the DNA-PK-dependent non-homologous end-joining (NHEJ) pathway by interacting with KU80. RBM14 is a RNA-binding protein (RBP) with low complexity domains, called intrinsically disordered proteins (IDPs), and it also physically interacts with PARP1. Furthermore, RBM14 is recruited to DNA double-strand breaks (DSBs) in a poly(ADP-ribose) (PAR)-dependent manner (unpublished data). DNA-dependent PARP1 (poly-(ADP) ribose polymerase 1) makes key contributions in the DNA damage response (DDR) network. RBM14 therefore plays an important role in a PARP-dependent DSB repair process. Most recently, it was shown that the other RBPs with intrinsically disordered domains are recruited to DNA damage sites in a PAR-dependent manner, and that these RBPs form liquid compartments (also known as "liquid-demixing"). Among the PAR-associated IDPs are FUS/TLS (fused in sarcoma/translocated in sarcoma), EWS (Ewing sarcoma), TARF15 (TATA box-binding protein-associated factor 68 kDa) (also called FET proteins), a number of heterogeneous nuclear ribonucleoproteins (hnRNPs), and RBM14. Importantly, various point mutations within the FET genes have been implicated in pathological protein aggregation in neurodegenerative diseases, specifically with amyotrophic lateral sclerosis (ALS), and frontotemporal lobe degeneration (FTLD). The FET proteins also frequently exhibit gene translocation in human cancers, and emerging evidence shows their physical interactions with DDR proteins and thus implies their involvement in the maintenance of genome stability.
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PMID:Roles of RNA-Binding Proteins in DNA Damage Response. 2711 Jul 71

Aquaporins (AQPs) are water channel proteins robustly expressed in the central nervous system (CNS). A number of previous studies described the cellular expression sites and investigated their major roles and function in the brain and spinal cord. Among thirteen different mammalian AQPs, AQP1 and AQP4 have been mainly studied in the CNS and evidence has been presented that they play important roles in the pathogenesis of CNS injury, edema and multiple diseases such as multiple sclerosis, neuromyelitis optica spectrum disorders, amyotrophic lateral sclerosis, glioblastoma multiforme, Alzheimer's disease and Parkinson's disease. The objective of this review is to highlight the current knowledge about AQPs in the spinal cord and their proposed roles in pathophysiology and pathogenesis related to spinal cord lesions and injury.
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PMID:Aquaporins in the Spinal Cord. 2794 18

Excitatory amino acid transporter 2 (EAAT2) is the predominant astrocyte glutamate transporter involved in the reuptake of the majority of the synaptic glutamate in the mammalian central nervous system (CNS). Gene expression can be altered without changing DNA sequences through epigenetic mechanisms. Mechanisms of epigenetic regulation, include DNA methylation, post-translational modifications of histones, chromatin remodeling, and small non-coding RNAs. This review is focused on neurological disorders, such as glioblastoma multiforme (GBM), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), bipolar disorder (BD), and neuroHIV where there is evidence that epigenetics plays a role in the reduction of EAAT2 expression. The emerging field of pharmaco-epigenetics provides a novel avenue for epigenetics-based drug therapy. This review highlights findings on the role of epigenetics in the regulation of EAAT2 in different neurological disorders and discusses the current pharmacological approaches used and the potential use of novel therapeutic approaches to induce EAAT2 expression in neurological disorders using CRISPR/Cas9 technology.
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PMID:Epigenetic Regulation of Excitatory Amino Acid Transporter 2 in Neurological Disorders. 3192 Jun 79