title: Death Associated Protein Kinase (DAPK) -mediated neurodegenerative mechanisms in nematode excitotoxicity.
abstract: BACKGROUND
  Excitotoxicity (the toxic overstimulation of neurons by the excitatory transmitter Glutamate) is a central process in widespread neurodegenerative conditions such as brain ischemia and chronic neurological diseases. Many mechanisms have been suggested to mediate excitotoxicity, but their significance across diverse excitotoxic scenarios remains unclear. Death Associated Protein Kinase (DAPK), a critical molecular switch that controls a range of key signaling and cell death pathways, has been suggested to have an important role in excitotoxicity. However, the molecular mechanism by which DAPK exerts its effect is controversial. A few distinct mechanisms have been suggested by single (sometimes contradicting) studies, and a larger array of potential mechanisms is implicated by the extensive interactome of DAPK.
  
  
  RESULTS
  Here we analyze a well-characterized model of excitotoxicity in the nematode C. elegans to show that DAPK is an important mediator of excitotoxic neurodegeneration across a large evolutionary distance. We further show that some proposed mechanisms of DAPK's action (modulation of synaptic strength, involvement of the DANGER-related protein MAB-21, and autophagy) do not have a major role in nematode excitotoxicity. In contrast, Pin1/PINN-1 (a DAPK interaction-partner and a peptidyl-prolyl isomerase involved in chronic neurodegenerative conditions) suppresses neurodegeneration in our excitotoxicity model.
  
  
  CONCLUSIONS
  Our studies highlight the prominence of DAPK and Pin1/PINN-1 as conserved mediators of cell death processes in diverse scenarios of neurodegeneration.
authors.affiliation: Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education (SBE), City College of New York (CCNY), The City University of New York (CUNY), New York, NY, USA. delrosariojohns@gmail.com.|MS program in Biology, CCNY, CUNY, New York, NY, USA. delrosariojohns@gmail.com.
authors.forename: John S
authors.initials: JS
authors.lastname: Del Rosario
authors.affiliation: Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education (SBE), City College of New York (CCNY), The City University of New York (CUNY), New York, NY, USA. kfeldmann@gc.cuny.edu.|PhD program in Neuroscience, the CUNY Graduate Center, New York, NY, USA. kfeldmann@gc.cuny.edu.
authors.forename: Katherine Genevieve
authors.initials: KG
authors.lastname: Feldmann
authors.affiliation: Undergraduate program in Biology, CCNY, CUNY, New York, NY, USA. niloyny945@yahoo.com.
authors.forename: Towfiq
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: Undergraduate program in Biochemistry, CCNY, CUNY, New York, NY, USA. uzairamjad210@yahoo.com.
authors.forename: Uzair
authors.initials: U
authors.lastname: Amjad
authors.affiliation: MS program in Biology, CCNY, CUNY, New York, NY, USA. bko0901@gmail.com.|Undergraduate program in Biology, CCNY, CUNY, New York, NY, USA. bko0901@gmail.com.
authors.forename: BakKeung
authors.initials: B
authors.lastname: Ko
authors.affiliation: Undergraduate program in Biology, CCNY, CUNY, New York, NY, USA. joonimay@gmail.com.
authors.forename: JunHyung
authors.initials: J
authors.lastname: An
authors.affiliation: Undergraduate program in Biology, CCNY, CUNY, New York, NY, USA. tmahmud03@gmail.com.
authors.forename: Tauhid
authors.initials: T
authors.lastname: Mahmud
authors.affiliation: Bs/MD program, Sophie Davis SBE, CCNY, CUNY, New York, NY, USA. msalama035@yahoo.com.
authors.forename: Maha
authors.initials: M
authors.lastname: Salama
authors.affiliation: Bs/MD program, Sophie Davis SBE, CCNY, CUNY, New York, NY, USA. shirlmei@yahoo.com.
authors.forename: Shirley
authors.initials: S
authors.lastname: Mei
authors.affiliation: Bs/MD program, Sophie Davis SBE, CCNY, CUNY, New York, NY, USA. dasem111@yahoo.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Asemota
authors.affiliation: Department of Physiology, Pharmacology, and Neuroscience, Sophie Davis School of Biomedical Education (SBE), City College of New York (CCNY), The City University of New York (CUNY), New York, NY, USA. imano@ccny.cuny.edu.|PhD program in Neuroscience, the CUNY Graduate Center, New York, NY, USA. imano@ccny.cuny.edu.
authors.forename: Itzhak
authors.initials: I
authors.lastname: Mano
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D064550:Death-Associated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D018698:Glutamic Acid / Q000633:toxicity*; D006257:Head; D008124:Locomotion / Q000502:physiology; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009410:Nerve Degeneration; D009474:Neurons / Q000201:enzymology*; D009498:Neurotoxins / Q000633:toxicity*; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C098124:Mab-21 protein, C elegans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009498:Neurotoxins; D018698:Glutamic Acid; C112443:UNC-51 protein, C elegans; D064550:Death-Associated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019696:Peptidylprolyl Isomerase