title: Therapeutic potential of N-acetyl-glucagon-like peptide-1 in primary motor neuron cultures derived from non-transgenic and SOD1-G93A ALS mice.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the death of motor neurons (MN) in the motor cortex, brain stem, and spinal cord. In the present study, we established an ALS in vitro model of purified embryonic MNs, derived from non-transgenic and mutant SOD1-G93A transgenic mice, the most commonly used ALS animal model. MNs were cultured together with either non-transgenic or mutant SOD1-G93A astrocyte feeder layers. Cell viability following exposure to kainate as excitotoxic stimulus was assessed by immunocytochemistry and calcium imaging. We then examined the neuroprotective effects of N-acetyl-GLP-1(7-34) amide (N-ac-GLP-1), a long-acting, N-terminally acetylated, C-terminally truncated analog of glucagon-like peptide-1 (GLP-1). GLP-1 has initially been studied as a treatment for type II diabetes based on its function as insulin secretagogue. We detected neuroprotective effects of N-ac-GLP-1 in our in vitro system, which could be attributed to an attenuation of intracellular calcium transients, not only due to these antiexcitotoxic capacities but also with respect to the increasing knowledge about metabolic deficits in ALS which could be positively influenced by N-ac-GLP-1, this compound represents an interesting novel candidate for further in vivo evaluation in ALS.
authors.affiliation: Department of Neurology, Hannover Medical School, OE 7210, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Sarah
authors.initials: S
authors.lastname: Knippenberg
authors.forename: Nadine
authors.initials: N
authors.lastname: Thau
authors.forename: Daniela
authors.initials: D
authors.lastname: Ragancokova
authors.forename: Sonja
authors.initials: S
authors.lastname: Körner
authors.forename: Dongya
authors.initials: D
authors.lastname: Huang
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dengler
authors.forename: Klaus
authors.initials: K
authors.lastname: Döhler
authors.forename: Susanne
authors.initials: S
authors.lastname: Petri
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005470:Fluorometry; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology / Q000627:therapeutic use*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009498:Neurotoxins / Q000633:toxicity; D018027:Receptors, Glucagon / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
chemical_list: C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D013482:Superoxide Dismutase; D007608:Kainic Acid; D002118:Calcium