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  • onset
  • Clinically, four phenotypes are distinguished within the continuous spectrum of disease severity based on the age of onset and the highest motor milestone ever achieved. (clinicaltrials.gov)
  • disease
  • For SMAII/III patients over 2 years of age, we will additionally administer the Hammersmith SMA functional motor scale (H-SMA-FMS), a disease-specific instrument. (clinicaltrials.gov)
  • There is an inverse correlation between SMN copy number and disease severity, presumably mediated by levels of full length SMN protein. (clinicaltrials.gov)
  • encodes
  • The XNP/ATR-X transcript encodes a predicted 2492 amino acid protein which harbours a nuclear localisation signal, three C 2 -C 2 zinc finger motifs, a coiled coil domain, and seven conserved "helicase" motifs found in DNA stimulated ATPase and DNA helicases of the SNF2/SWI2 protein family. (bmj.com)
  • mutations
  • SMA is caused by loss of the full-length protein that results primarily from deletions or mutations in exon-7, suggesting its critical importance for SMN function ( Wirth, 2000 ). (jneurosci.org)
  • Previous studies have shown that 65% of mutations of XNP have been found within the zinc finger domain (encoded by exons 7, 8, and the beginning of exon 9) while 35% of the mutations have been found in the helicase domain extending over 3 kb at the C-terminus of the protein. (bmj.com)
  • Our aims were to understand the function of the XNP/ATR-X protein better, with specific attention to the functional consequences of mutations to the zinc finger domain. (bmj.com)
  • Disease
  • The upregulation of a specific subset of BH3-only proteins, including Bid, DP5/Hrk, and BNip3L, in reactive astrocytes suggests that these proteins may execute a novel non-apoptotic function within astrocytes to promote ALS disease progression, thus providing a new potential target for therapeutic intervention. (frontiersin.org)
  • We use the baker's yeast, Saccharomyces cerevisiae, as a model system to study the cell biology underpinning protein-misfolding diseases like Parkinson's disease and ALS. (stanford.edu)
  • Our long-term goal is to identify the critical genes and cellular pathways affected by misfolded human disease proteins. (stanford.edu)
  • Encouraged by the power of the yeast system to gain insight into α-synuclein biology, we are creating new yeast models to study additional protein-misfolding disorders, including Alzheimer's disease and ALS. (stanford.edu)
  • We recently developed a yeast model to study the ALS disease protein TDP-43 (Johnson et al. (stanford.edu)
  • We are now using these models to perform high-throughput genetic and small molecule screens to elucidate the molecular pathways that regulate the function of these disease proteins and control their conversion to a pathological conformation. (stanford.edu)
  • Interestingly, one of the hits from our yeast TDP-43 genetic modifier screen, PBP1, is the homolog of a human neurodegenerative disease protein, ataxin 2. (stanford.edu)
  • However, the MNs of the brainstem oculomotor (ON), trochlear and abducens nuclei (also called jointly extraocular motor nuclei or oculomotor nuclei) are much more ALS-resistant than those of other cranial nerve nuclei and of the spinal cord (SC) anterior horns, and their degeneration and loss over the course of the disease is much slower [18, (termedia.pl)
  • genes
  • Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development. (genecards.org)
  • 1. The genes and pathways that are able to modify TDP-43 toxicity in yeast are now good candidates for evaluation as genetic contributors to ALS and related disorders in humans (e.g., see ataxin 2 below). (stanford.edu)
  • gems
  • Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs). (genecards.org)
  • fibrillarin
  • Fibrillarin is an essential protein that is well known as a molecular marker of transcriptionally active RNA polymerase I. Fibrillarin methyltransferase activity is the primary known source of methylation for more than 100 methylated sites involved in the first steps of preribosomal processing and required for structural ribosome stability. (embl-heidelberg.de)
  • Here, we show fibrillarin domain conservation, structure and interacting molecules in different cellular processes as well as with several viral proteins during virus infection. (embl-heidelberg.de)
  • We previously showed that SMN relocated to damaged interphase centromeres, together with the Cajal-body-associated proteins coilin and fibrillarin, during the so-called interphase centromere damage response (iCDR). (embl-heidelberg.de)
  • pathology
  • We found that lowering levels of ataxin 2 in mouse, either by knockout or with antisense oligonucleotides (ASOs) can markedly extend survival and reduce pathology in TDP-43 transgenic mice (Becker et al. (stanford.edu)
  • inducible
  • explored the temporal requirement for survival motoneuron (SMN) proteins using an inducible deletion strategy in mice. (jci.org)
  • We focused our attention on HSP70-2, an inducible chaperon induced under stress conditions. (jove.com)
  • interaction
  • We have validated this genetic interaction in the fly nervous system (in collaboration with Nancy Bonini at PENN), used biochemistry to show the proteins physically associate in an RNA-dependent manner. (stanford.edu)
  • diseases
  • A role for polyQ expansions in ataxin 2 in ALS and related diseases is being evaluated by us and others in independent patient populations worldwide. (stanford.edu)
  • genetic
  • Insulin-like growth factor-binding protein 7 (IGFBP7), a novel biomarker for tumor fibroblasts in epithelial cancer, has also been detected in CAFs through genetic screenings and immunohistochemical studies. (spandidos-publications.com)
  • apoptosis
  • Several studies have provided compelling evidence for mitochondrial oxidative stress, mitochondrial dysfunction, and intrinsic apoptosis as significant factors in the motor neuron death that underlies ALS. (frontiersin.org)
  • Syndrome
  • Some X-linked dominant conditions such as Rett syndrome, incontinentia pigmenti type 2 and Aicardi syndrome are usually fatal in males either in utero or shortly after birth, and are therefore predominantly seen in females. (prezi.com)
  • western blot
  • We used monoclonal antibodies directed against the XNP/ATR-X protein and performed immunocytochemical and western blot analyses, which showed altered or absent XNP/ATR-X expression in cells of affected patients. (bmj.com)
  • human
  • Fibroblast activation protein α (FAPα) is a cytomembrane protein that is selectively expressed by activated CAFs in various types of human epithelial cancer ( 13 ). (spandidos-publications.com)
  • Monkey and human studies [44,revealed that the abundance of parvalbumin in MNs, which protects them from excess intracellular Ca2+ ions, a key mediator of glutamate toxicity, is much higher in the aforesaid three extraocular motor nuclei than that in other brainstem MN nuclei. (termedia.pl)
  • motif
  • LacdiNAc (GalNAcβ1-4GlcNAc) is a major motif in N-glycan structures of the chicken eggshell protein ovocleidin-116. (mpg.de)
  • distinct
  • A major question is whether SMN has distinct functions in neurons, which when disrupted, could impair neuronal growth and differentiation. (jneurosci.org)
  • interphase
  • 16 Lastly, it has been reported that XNP/ATR-X is a nuclear protein closely associated with the nuclear matrix at interphase and during mitosis the protein is found close to pericentromeric chromatin. (bmj.com)
  • mechanisms
  • Since dealing with misfolded proteins is an ancient problem, we hypothesize that the mechanisms employed to cope with them are likely conserved from yeast to man. (stanford.edu)
  • belongs
  • SMN belongs to the Tudor domain protein family, whose members are known to interact with methylated arginine (R) or lysine (K) residues. (embl-heidelberg.de)