論文 - 詳細
| RRC ID | 45552 |
|---|---|
| 著者 | Del Rosario JS, Feldmann KG, Ahmed T, Amjad U, Ko B, An J, Mahmud T, Salama M, Mei S, Asemota D, Mano I. |
| タイトル | Death Associated Protein Kinase (DAPK) -mediated neurodegenerative mechanisms in nematode excitotoxicity. |
| ジャーナル | BMC Neurosci |
| 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. |
| 巻・号 | 16 |
| ページ | 25 |
| 公開日 | 2015-4-23 |
| DOI | 10.1186/s12868-015-0158-2 |
| PII | 10.1186/s12868-015-0158-2 |
| PMID | 25899010 |
| PMC | PMC4414438 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Death / physiology* Death-Associated Protein Kinases / genetics Death-Associated Protein Kinases / metabolism* Gene Knockout Techniques Glutamic Acid / toxicity* Head Locomotion / physiology NIMA-Interacting Peptidylprolyl Isomerase Nerve Degeneration* Neurons / enzymology* Neurotoxins / toxicity* Peptidylprolyl Isomerase / genetics Peptidylprolyl Isomerase / metabolism Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism |
| IF | 2.811 |
| 引用数 | 15 |
| WOS 分野 | NEUROSCIENCES |
| リソース情報 | |
| 線虫 | tm2235 |