Beclin1 decreases the RIPA-insoluble fraction of amyotrophic lateral sclerosis-linked SOD1 mutant via autophagy

Publication date: Available online 12 October 2018Source: Neuroscience LettersAuthor(s): Yan-Ming Wei, Bo HanAbstractMany neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), are characterised by the intracellular appearance of protein aggregates or insoluble materials. Accelerated removal of related toxic proteins might be beneficial for these diseases. Here we describe an inducible role of Beclin1, an essential regulator for autophagy, in degradation of the familial ALS-linked Cu/Zn superoxide dismutase 1 (SOD1) mutant. We confirmed that the SOD1 mutant exhibited an increased RIPA (radioimmune precipitation assay buffer, containing NP40 and sodium deoxycholate)-insolubility compared with SOD1 wild-type (WT). Also, the insoluble fraction formed by SOD1 mutant was greatly reduced by coexpressing Beclin1 in both neuronal and non-neuronal cell lines. Pharmacological inhibition of autophagy diminished the effect of Beclin1 and resulted in an accumulation of insoluble SOD1. Our results support the role of Beclin1 in the involvement of autophagic degradation of SOD1 mutant. We propose Beclin1 enhances autophagy and presents a possible therapeutic strategy for familial ALS.
Source: Neuroscience Letters - Category: Neuroscience Source Type: research

Related Links:

In conclusion, Axon-seq provides an improved method for RNA-seq of axons, increasing our understanding of peripheral axon biology and identifying therapeutic targets in motor neuron disease.Graphical Abstract
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
Conclusion: We have investigated 217 differential pathways and 21 significant differential pathways between SALS and normal controls based on network strategy. The findings might provide potential biomarkers for detection and therapy of SALS clinically and give great insights to reveal molecular mechanism underlying this disease. However, how these pathways cooperated with each other is still not clear, and future study should focus on this aspect.
Source: Journal of Cancer Research and Therapeutics - Category: Cancer & Oncology Authors: Source Type: research
Abstract Hepatocyte growth factor is an endogenous pleiotropic factor shown to act as a potent neuroprotectant against disease progression in animal models of amyotrophic lateral sclerosis, which is a devastating, adult-onset motor neuron disease. To evaluate the safety, tolerability, and pharmacokinetics of recombinant 5-residue-deleted human hepatocyte growth factor (KP-100) injected intrathecally through an implantable catheter connected to a subcutaneous port, we conducted a first-in-human phase I trial of intrathecal KP-100 in 15 Japanese patients with amyotrophic lateral sclerosis. The regimen was a single i...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research
Authors: Torres-Navarro I PMID: 30502297 [PubMed - as supplied by publisher]
Source: Medicina Clinica - Category: General Medicine Tags: Med Clin (Barc) Source Type: research
In conclusion, this is the first report to show that pyroptotic cell death occurs in the aging brain and that the inflammasome can be a viable target to decrease the oxidative stress that occurs as a result of aging. Reducing Levels of Protein Manufacture Slows Measures of Aging in Nematodes https://www.fightaging.org/archives/2018/12/reducing-levels-of-protein-manufacture-slows-measures-of-aging-in-nematodes/ Researchers here demonstrate that an antibiotic slows aging in nematode worms, providing evidence for it to work through a reduction in protein synthesis. Beyond a slowing of aging, one of the con...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Diagnostic criteria for amyotrophic lateral sclerosis (ALS) have been developed to standardise diagnosis and patient recruitment in trials. A research group of the World Federation of Neurology (WFN) devised the “El Escorial criteria” (EEC) (Brooks et al., 1994), which were later modified to increase their diagnostic sensitivity as the “revised El Escorial Criteria” (rEEC) (Brooks et al., 2000) with the objective of encouraging earlier inclusion in trials (Ross et al., 1998). The rEEC have been foun d to have high specificity, but to lack sensitivity, thus failing to promote earlier patient inclusio...
Source: Clinical Neurophysiology - Category: Neuroscience Authors: Source Type: research
CONCLUSIONS We identified a novel frameshift mutation associated with JALS. JALS and generally typical ALS, with the same FUS mutation, can appear in a family and present a phenomenon of anticipation. For diagnosis of central nervous system degeneration in adolescents with bulbar symptoms, great attention should be paid to JALS. PMID: 30507891 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Marta Simone, Antonio Trabacca, Elena Panzeri, Luciana Losito, Andrea Citterio, Maria Teresa Bassi
Source: Frontiers in Neurology - Category: Neurology Source Type: research
CONCLUSIONS: 50-Hz MF affects iron homeostasis in the in vitro SOD1G93A ALS model. PMID: 30513241 [PubMed - as supplied by publisher]
Source: International Journal of Radiation Biology - Category: Radiology Tags: Int J Radiat Biol Source Type: research
Condition:   Amyotrophic Lateral Sclerosis Interventions:   Biological: Fecal microbiota transplantation;   Biological: Placebo Sponsors:   Azienda Ospedaliero-Universitaria di Modena;   University of Modena and Reggio Emilia;   Catholic University of the Sacred Heart;   Campus Bio-Medico University;   Azienda Ospedaliero-Universitaria Careggi;   Azienda Ospedaliera di Perugia;   University of Chieti;   University of Flor...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
More News: ALS | Brain | Neurology | Neuroscience | Sodium | Toxicology