For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
7
views
85
references
 Top references
cited by
30
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      1,230
      similar
       All similar
      • Record: found
      • Abstract: not found
      • Article: not found

      Administration of 17β-Estradiol Improves Motoneuron Survival and Down-regulates Inflammasome Activation in Male SOD1(G93A) ALS Mice

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease manifested by the progressive loss of upper and lower motoneurons. The pathomechanism of ALS is complex and not yet fully understood. Neuroinflammation is believed to significantly contribute to disease progression. Inflammasome activation was recently shown in the spinal cord of human sporadic ALS patients and in the SOD1(G93A) mouse model for ALS. In the present study, we investigated the neuroprotective and anti-inflammatory effects of 17β-estradiol (E2) treatment in pre-symptomatic and symptomatic male SOD1(G93A) mice. Symptomatic mice with E2 substitution exhibited improved motor performance correlating with an increased survival of motoneurons in the lumbar spinal cord. Expression of NLRP3 inflammasome proteins and levels of activated caspase 1 and mature interleukin 1 beta were significantly reduced in SOD1(G93A) mice supplemented with E2.

          Related collections

          Most cited references85

          • Record: found
          • Abstract: found
          • Article: not found

          Inflammasomes in the CNS.

          John Walsh, Daniel A. Muruve, Christopher Power (2014)
          Microglia and macrophages in the CNS contain multimolecular complexes termed inflammasomes. Inflammasomes function as intracellular sensors for infectious agents as well as for host-derived danger signals that are associated with neurological diseases, including meningitis, stroke and Alzheimer's disease. Assembly of an inflammasome activates caspase 1 and, subsequently, the proteolysis and release of the cytokines interleukin-1β and interleukin-18, as well as pyroptotic cell death. Since the discovery of inflammasomes in 2002, there has been burgeoning recognition of their complexities and functions. Here, we review the current understanding of the functions of different inflammasomes in the CNS and their roles in neurological diseases.
          Article 0 comments Cited 264 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Genetics of amyotrophic lateral sclerosis: an update

            Tian Chen, Pavani Sayana, Xiaojie Zhang … (2013)
            Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder involving both upper motor neurons (UMN) and lower motor neurons (LMN). Enormous research has been done in the past few decades in unveiling the genetics of ALS, successfully identifying at least fifteen candidate genes associated with familial and sporadic ALS. Numerous studies attempting to define the pathogenesis of ALS have identified several plausible determinants and molecular pathways leading to motor neuron degeneration, which include oxidative stress, glutamate excitotoxicity, apoptosis, abnormal neurofilament function, protein misfolding and subsequent aggregation, impairment of RNA processing, defects in axonal transport, changes in endosomal trafficking, increased inflammation, and mitochondrial dysfunction. This review is to update the recent discoveries in genetics of ALS, which may provide insight information to help us better understanding of the disease neuropathogenesis.
            Article 0 comments Cited 138 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Microglia in ALS: the good, the bad, and the resting.

              Jenny Henkel, David R Beers, Weihua Zhao … (2009)
              Inflammation, including microglial activation and T cell infiltration, is a neuropathological hallmark of amyotrophic lateral sclerosis (ALS), a rapidly progressing neurodegenerative disease. The identification of mutations in the gene for Cu2+/Zn2+ superoxide dismutase (SOD1) from patients with an inherited form of ALS enabled the creation of transgenic mice overexpressing mutant forms of SOD1 (mSOD1) which develop a motoneuron disease that resembles the disease seen in ALS patients. These transgenic mice display similar inflammatory reactions at sites of motoneuron injury as detected in ALS patients, enabling the observation that this inflammation is not simply a late consequence of motoneuron degeneration, but actively contributes to the balance between neuroprotection and neurotoxicity. The microglial and T cell activation states influence the rate of disease progression. Initially, microglia and T cells can slow disease progression, while they may later contribute to the acceleration of disease. Accumulation of intracellular and extracellular misfolded mSOD1 may be key events regulating the transformation from neuroprotective alternatively activated M2 microglia to cytotoxic classically activated M1 microglia. Intracellular and extracellular mSOD1 utilizing different pathways may enhance the production and release of reactive oxygen species (ROS) and augment the inflammatory cytokine cascade from microglia. These ROS and cytokines may increase the susceptibility of motoneurons to glutamate toxicity and inhibit the function and expression of astrocytic glutamate transporters resulting in further neurotoxicity. Thus, the cumulative evidence suggests that inflammation plays a central role in ALS and manipulating these microglial effector functions may potentially modify the outcome of this devastating disease.
              Article 0 comments Cited 136 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Title: Molecular Neurobiology
                Abbreviated Title: Mol Neurobiol
                Publisher: Springer Nature
                ISSN (Print): 0893-7648
                ISSN (Electronic): 1559-1182
                Publication date Created: December 2017
                Publication date (Electronic): December 12 2016
                Publication date (Print): December 2017
                Volume: 54
                Issue: 10
                Pages: 8429-8443
                Article
                DOI: 10.1007/s12035-016-0322-4
                PubMed ID: 27957680
                SO-VID: 516928e7-513d-4f74-9647-beb1d3f26184
                Copyright © © 2017
                License:

                http://www.springer.com/tdm

                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content1,230

                See all similar

                Cited by30

                See all cited by

                Most referenced authors1,073

                See all reference authors