Abstract:
:The etiology of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder characterized by progressive muscle weakness and spasticity, remains largely unknown. Approximately 5-10% of cases are familial, and of those, 15-20% are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Mutations of the SOD1 gene interrupt cellular homeostasis and contribute to cellular toxicity evoked by the presence of altered SOD1, along with other toxic species, such as advanced glycation end products (AGEs). AGEs trigger activation of their chief cell surface receptor, RAGE (receptor for advanced glycation end products), and induce RAGE-dependent cellular stress and inflammation in neurons, thereby affecting their function and leading to apoptosis. Here, we show for the first time that the expression of RAGE is higher in the SOD1 transgenic mouse model of ALS vs. wild-type mouse spinal cord. We tested whether pharmacological blockade of RAGE may delay the onset and progression of disease in this mouse model. Our findings reveal that treatment of SOD1 transgenic mice with soluble RAGE (sRAGE), a natural competitor of RAGE that sequesters RAGE ligands and blocks their interaction with cell surface RAGE, significantly delays the progression of ALS and prolongs life span compared to vehicle treatment. We demonstrate that in sRAGE-treated SOD1 transgenic animals at the final stage of the disease, a significantly higher number of neurons and lower number of astrocytes is detectable in the spinal cord. We conclude that RAGE antagonism may provide a novel therapeutic strategy for ALS intervention.
journal_name
Front Cell Neuroscijournal_title
Frontiers in cellular neuroscienceauthors
Juranek JK,Daffu GK,Geddis MS,Li H,Rosario R,Kaplan BJ,Kelly L,Schmidt AMdoi
10.3389/fncel.2016.00117subject
Has Abstractpub_date
2016-05-09 00:00:00pages
117issn
1662-5102journal_volume
10pub_type
杂志文章abstract::Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connection...
journal_title:Frontiers in cellular neuroscience
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journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2013.00147
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abstract::Alzheimer disease is characterized by a progressive cognitive deficit and may be associated with an aberrant hyperexcitability of the neuronal network. Notoginsenoside R1 (R1), a major activity ingredient from Panax notoginseng, has demonstrated favorable changes in neuronal plasticity and induced neuroprotective effe...
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abstract::In the primary motor cortex (M1), layer 5 projection neurons signal directly to distant motor structures to drive movement. Despite their pivotal position and acknowledged diversity these neurons are traditionally separated into broad commissural and corticofugal types, and until now no attempt has been made at resolv...
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abstract::Variants near the ATP-binding cassette transporter A1 (ABCA1) gene are associated with elevated intraocular pressure and newly discovered risk factors for glaucoma. Previous studies have shown an association between ABCA1 deficiency and retinal inflammation. Using a mouse model of ischemia-reperfusion (IR) induced by ...
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journal_title:Frontiers in cellular neuroscience
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doi:10.3389/fncel.2018.00352
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journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
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journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
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journal_title:Frontiers in cellular neuroscience
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doi:10.3389/fncel.2018.00341
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abstract::Germinal matrix hemorrhage (GMH) is a serious complication in extremely preterm infants associated with neurological deficits and mortality. The purpose of the present study was to develop and characterize a grade III and IV GMH model in postnatal day 5 (P5) rats, the equivalent of preterm human brain maturation. P5 W...
journal_title:Frontiers in cellular neuroscience
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abstract::In the last decade, there is an increasing application of induced pluripotent stem cells (iPSCs) for disease modeling. The iPSC technology enables the study of patient-specific neuronal cell lines in vitro to evaluate dysfunction at the cellular level and identify the responsible genetic factors. This approach might b...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00321
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journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2019.00373
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abstract::Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterized by the progressive loss of motor neurons. The cause of this selective neuronal death is unknown, but transcriptional dysregulation is recently emerging as an important factor. The physical substrate for the regulation of the transc...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2013.00243
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journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00168
更新日期:2018-06-15 00:00:00
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journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
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journal_title:Frontiers in cellular neuroscience
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journal_title:Frontiers in cellular neuroscience
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journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
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journal_title:Frontiers in cellular neuroscience
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journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
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