| http://purl.uniprot.org/citations/32242285 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32242285 | http://www.w3.org/2000/01/rdf-schema#comment | "L-serine is a naturally occurring dietary amino acid that has recently received renewed attention as a potential therapy for the treatment of amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), hereditary sensory autonomic neuropathy type I (HSAN1), and sleep induction and maintenance. We have previously reported L-serine functions as a competitive inhibitor of L-BMAA toxicity in cell cultures and have since progressed to examine the neuroprotective effects of L-serine independent of L-BMAA-induced neurotoxicity. For example, in a Phase I, FDA-approved human clinical trial of 20 ALS patients, our lab reported 30 g L-serine/day was safe, well-tolerated, and slowed the progression of the disease in a group of 5 patients. Despite increasing evidence for L-serine being useful in the clinic, little is known about the mechanism of action of the observed neuroprotection. We have previously reported, in SH-SY5Y cell cultures, that L-serine alone can dysregulate the unfolded protein response (UPR) and increase the translation of the chaperone protein disulfide isomerase (PDI), and these mechanisms may contribute to the clearance of mis- or unfolded proteins. Here, we further explore the pathways involved in protein clearance when L-serine is present in low and high concentrations in cell culture. We incubated SH-SY5Y cells in the presence and absence of L-serine and measured changes in the activity of proteolytic enzymes from the autophagic-lysosomal system, cathepsin B, cathepsin L, and arylsulfatase and specific activities of the proteasome, peptidylglutamyl-peptide hydrolyzing (PGPH) (also called caspase-like), chymotrypsin, and trypsin-like. Under our conditions, we report that L-serine selectively induced the activity of autophagic-lysosomal enzymes, cathepsins B and L, but not any of the proteasome-hydrolyzing activities. To enable comparison with previous work, we also incubated cells with L-BMAA and report no effect on the activity of the autophagic lysosomes or the proteasomes. We also developed an open-source script for the automation of linear regression calculations of kinetic data. Autophagy impairment or failure is characteristic of many neurodegenerative disease; thus, activation of autophagic-lysosomal proteolysis may contribute to the neuroprotective effect of L-serine, which has been reported in cell culture and human clinical trials."xsd:string |
| http://purl.uniprot.org/citations/32242285 | http://purl.org/dc/terms/identifier | "doi:10.1007/s12640-020-00168-2"xsd:string |
| http://purl.uniprot.org/citations/32242285 | http://purl.uniprot.org/core/author | "Carney J.M."xsd:string |
| http://purl.uniprot.org/citations/32242285 | http://purl.uniprot.org/core/author | "Dunlop R.A."xsd:string |
| http://purl.uniprot.org/citations/32242285 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/32242285 | http://purl.uniprot.org/core/name | "Neurotox Res"xsd:string |
| http://purl.uniprot.org/citations/32242285 | http://purl.uniprot.org/core/pages | "17-26"xsd:string |
| http://purl.uniprot.org/citations/32242285 | http://purl.uniprot.org/core/title | "Mechanisms of L-Serine-Mediated Neuroprotection Include Selective Activation of Lysosomal Cathepsins B and L."xsd:string |
| http://purl.uniprot.org/citations/32242285 | http://purl.uniprot.org/core/volume | "39"xsd:string |
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