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22.
Natsumi Furuta Kouki Makioka Yukio Fujita Masaki Ikeda Masamitsu Takatama Masaaki Matsuoka Koichi Okamoto 《Neuropathology》2013,33(4):397-404
Overexpression of BTBD10 (BTB/POZ domain‐containing protein 10) suppresses G93A‐superoxide dismutase 1 (SOD1)‐induced motor neuron death in a cell‐based amyotrophic lateral sclerosis (ALS) model. In the present study, paraffin sections of spinal cords from 13 patients with sporadic ALS and 10 with non‐ALS disorders were immunostained using a polyclonal anti‐BTBD10 antibody. Reduced BTBD10 expression in the anterior horn cells was more frequent in spinal cords from ALS patients than in cords from patients with non‐ALS disorders. We further investigated the relationship between the level of BTBD10 immunoreactivity and the morphology of the Golgi apparatus (GA) and the presence of phosphorylated TAR‐DNA‐binding protein 43 (pTDP‐43). Mirror sections of spinal cords from five sporadic ALS cases were immunostained with antibodies against BTBD10 and trans‐Golgi‐network (TGN)‐46 or pTDP‐43. Whereas 89.7–96.5% of the neurons with normal BTBD10 immunoreactivity showed normal GA morphology and no pTDP‐43 cytoplasmic aggregates, 86.2–94.3% of the neurons with reduced BTBD10 expression showed GA fragmentation and abnormal pTDP‐43 aggregates. These findings suggest that reduced BTBD10 expression is closely linked to the pathogenesis of sporadic ALS. 相似文献
23.
Human neurodegenrative diseases such as Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are caused by a loss of neurons and glia in the brain or spinal cord. Neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and stem cell‐based cell therapies for neurodegenerative diseases have been developed. A recent advance in generatioin of a new class of pluripotent stem cells, induced pluripotent stem cells (iPSCs), derived from patients' own skin fibroblasts, opens doors for a totally new field of personalized medicine. Transplantation of NSCs, neurons or glia generated from stem cells in animal models of neurodegenrative diseases, including PD, HD, ALS and AD, demonstrates clinical improvement and also life extension of these animals. Additional therapeutic benefits in these animals can be provided by stem cell‐mediated gene transfer of therapeutic genes such as neurotrophic factors and enzymes. Although further research is still needed, cell and gene therapy based on stem cells, particularly using neurons and glia derived from iPSCs, ESCs or NSCs, will become a routine treatment for patients suffering from neurodegenerative diseases and also stroke and spinal cord injury. 相似文献
24.
Stem cell factor‐activated bone marrow ameliorates amyotrophic lateral sclerosis by promoting protective microglial migration
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Tomoya Terashima Hideto Kojima Hiroshi Urabe Isamu Yamakawa Nobuhiro Ogawa Hiromichi Kawai Lawrence Chan Hiroshi Maegawa 《Journal of neuroscience research》2014,92(7):856-869
Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with motor neuron death. Several experimental treatments, including cell therapy using hematopoietic or neuronal stem cells, have been tested in ALS animal models, but therapeutic benefits have been modest. Here we used a new therapeutic strategy, bone marrow transplantation (BMT) with stem cell factor (SCF)‐ or FMS‐like tyrosine kinase 3 (flt3)‐activated bone marrow (BM) cells for the treatment of hSOD1(G93A) transgenic mice. Motor function and survival showed greater improvement in the SCF group than in the group receiving BM cells that had not been activated (BMT alone group), although no improvement was shown in the flt3 group. In addition, larger numbers of BM‐derived cells that expressed the microglia marker Iba1 migrated to the spinal cords of recipient mice compared with the BMT‐alone group. Moreover, after SCF activation, but not flt3 activation or no activation, the migrating microglia expressed glutamate transporter‐1 (GLT‐1). In spinal cords in the SCF group, inflammatory cytokines tumor necrosis factor‐α and interleukin‐1β were suppressed and the neuroprotective molecule insulin‐like growth factor‐1 increased relative to nontreatment hSOD1(G93A) transgenic mice. Therefore, SCF activation changed the character of the migrating donor BM cells, which resulted in neuroprotective effects. These studies have identified SCF‐activated BM cells as a potential new therapeutic agent for the treatment of ALS. © 2014 Wiley Periodicals, Inc. 相似文献
25.
Sandra Anne Banack Tracie Caller Patricia Henegan James Haney Amanda Murby James S. Metcalf James Powell Paul Alan Cox Elijah Stommel 《Toxins》2015,7(2):322-336
A cluster of amyotrophic lateral sclerosis (ALS) has been previously described to border Lake Mascoma in Enfield, NH, with an incidence of ALS approximating 25 times expected. We hypothesize a possible association with cyanobacterial blooms that can produce β-N-methylamino-l-alanine (BMAA), a neurotoxic amino acid implicated as a possible cause of ALS/PDC in Guam. Muscle, liver, and brain tissue samples from a Lake Mascoma carp, as well as filtered aerosol samples, were analyzed for microcystins (MC), free and protein-bound BMAA, and the BMAA isomers 2,4-diaminobutyric acid (DAB) and N-(2-aminoethyl)glycine (AEG). In carp brain, BMAA and DAB concentrations were 0.043 μg/g ± 0.02 SD and 0.01 μg/g ± 0.002 SD respectively. In carp liver and muscle, the BMAA concentrations were 1.28 μg/g and 1.27 μg/g respectively, and DAB was not detected. BMAA was detected in the air filters, as were the isomers DAB and AEG. These results demonstrate that a putative cause for ALS, BMAA, exists in an environment that has a documented cluster of ALS. Although cause and effect have not been demonstrated, our observations and measurements strengthen the association. 相似文献
26.
Manoj Kumar Jaiswal 《Medicinal research reviews》2019,39(2):733-748
Over the past decades, a multitude of experimental drugs have been shown to delay disease progression in preclinical animal models of amyotrophic lateral sclerosis (ALS) but failed to show efficacy in human clinical trials or are still waiting for approval under Phase I–III trials. Riluzole, a glutamatergic neurotransmission inhibitor, is the only drug approved by the USA Food and Drug Administration for ALS treatment with modest benefits on survival. Recently, an antioxidant drug, edaravone, developed by Mitsubishi Tanabe Pharma was found to be effective in halting ALS progression during early stages. The newly approved drug edaravone is a force multiplier for ALS treatment. This short report provides an overview of the two drugs that have been approved for ALS treatment and highlights an update on the timeline of drug development, how clinical trials were done, the outcome of these trials, primary endpoint, mechanism of actions, dosing information, administration, side effects, and storage procedures. Moreover, we also discussed the pressing issues and challenges of ALS clinical trials and drug developments as well as future outlook. 相似文献
27.
M. J. D. Anderson H. Oeljeschlager H. K. Müller-Hermelink W. Müller-Ruchholtz 《Journal of cancer research and clinical oncology》1981,101(1):101-107
Summary Absorption procedures which allow the production of a selectively cytotoxic anti-human lymphocyte serum are described. Although the production of a reagent whose reactivity is restricted exclusively to lymphocytes may be achieved by exhaustive absorption steps using fresh human erythrocytes, CML cells, and fetal liver cells, a more realistic alternative is the use of appropriately selected cultured human leukemia cell lines. Data are presented which show how these cell lines may be employed to selectively manipulate the crossreactivity spectrum of ALS.Pre-treatment of donor bone marrow cells prior to transplantation with a selectively lymphocytotoxic ALS has been shown to allow transplantation of bone marrow across major histocompatibility barriers in rodents without the occurrence of GvH reactions, and it is the purpose of the present investigations to show that an analogous anti-human ALS can be prepared which possesses the required degree of selectivity to allow its application for human bone marrow transplantation.Abbreviations ALS
anti-lymphocyte serum
- CFU-c
colony-forming unit, in vitro
- CFU-dc
colonyforming unit, diffusion chamber
- CML
chronic myelogenous leukemia
- FCS
fetal calf serum
- GvHR
graft-versus-host reaction
- MLC
mixed lymphocyte reaction
- SAL
selective anti-lymphocyte serum 相似文献
28.
Audrey Yi Tyan Peng Ira Agrawal Wan Yun Ho Yi-Chun Yen Ashley J. Pinter Jerry Liu Qi Xuan Cheryl Phua Katrianne Bethia Koh Jer-Cherng Chang Emma Sanford Jodie Hon Kiu Man Peiyan Wong David H. Gutmann Greg Tucker-Kellogg Shuo-Chien Ling 《Proceedings of the National Academy of Sciences of the United States of America》2020,117(46):29101
29.
Kourosh Rezania MD Ori Gottlieb MD Amy Guralnick MD Vivek Prachand MD Bobbie J. Sweitzer MD Wickii Vigneswaran MD Steven R. White MD Raymond P. Roos MD 《Muscle & nerve》2014,50(5):863-865
Introduction: Patients with amyotrophic lateral sclerosis (ALS) are prone to venous thromboembolism (VTE) and secondary complications. Because there is an increased incidence of VTE after surgical procedures, placement of a Diaphragm Pacing System (DPS) in ALS patients as treatment for respiratory muscle weakness could potentially increase the incidence of VTE, especially in patients with limited mobility. Methods: We implanted a DPS in 10 ALS patients who met the criteria for this procedure. They underwent a preoperative evaluation as recommended by the guidelines. Results: We report 2 patients with no symptoms of deep vein thrombosis (DVT) before the surgical procedure who then developed perioperative VTE. Conclusions: These patients highlight the need to consider preoperative screening for DVT and postoperative thromboprophylaxis in high‐risk ALS patients who undergo DPS placement. Muscle Nerve 50 : 863–865, 2014 相似文献
30.
Russell Lewis McLaughlin Kevin Patrick Kenna Alice Vajda Susan Byrne Daniel G. Bradley Orla Hardiman 《Neurobiology of aging》2014
Mutations in UBQLN2 have been shown to be a cause of dominant X-linked amyotrophic lateral sclerosis (ALS). Occurrences of mutations in this gene vary across ALS populations. We screened UBQLN2 for mutations in a final cohort of 150 Irish ALS patients. Individuals who were from families with male-to-male transmission or who carried pathogenic hexanucleotide repeat expansions in C9orf72 were excluded. Apart from common synonymous variation, no sequence variants in UBQLN2 were observed. Mutations in UBQLN2 are therefore not a frequent cause of ALS in the Irish population. 相似文献