title: Sterol regulatory element binding protein-1 (SREBP1) activation in motor neurons in excitotoxicity and amyotrophic lateral sclerosis (ALS): Indip, a potential therapeutic peptide.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons in which glutamatergic excitotoxicity may participate. A recently characterized downstream effector of glutamatergic excitotoxicity is the activation of the lipid transcription factor sterol regulatory element binding protein-1 (SREBP1). Here we report that in spinal cord tissues of transgenic mouse model, G93A, as well as post-mortem spinal cord specimens of human familial and sporadic ALS, significant activation of SREBP1 following drastic degradation of ER membrane resident protein Insig-1. A TAT-fused short peptide (Indip) to prevent Insig-1 degradation and subsequent SREBP1 activation significantly protected cultured spinal cord neurons against glutamate-induced excitotoxicity. Indip or other SREBP1-pathway modulating compounds may prove beneficial in ALS.
authors.affiliation: Brain Research Centre, University of British Columbia, Vancouver, Canada. changiz.taghibiglou@usask.ca
authors.forename: Changiz
authors.initials: C
authors.lastname: Taghibiglou
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mackenzie
authors.forename: Yu Tian
authors.initials: YT
authors.lastname: Wang
authors.forename: Neil R
authors.initials: NR
authors.lastname: Cashman
mesh_terms: D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D019610:Cytoprotection; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C568329:Indip peptide; C506119:Insig1 protein, mouse; D008565:Membrane Proteins; D009498:Neurotoxins; D010455:Peptides; D051780:Sterol Regulatory Element Binding Protein 1; D018698:Glutamic Acid