PMID- 21565252
OWN - NLM
STAT- MEDLINE
DCOM- 20111107
LR  - 20211203
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 498
IP  - 1
DP  - 2011 Jul 1
TI  - A Caenorhabditis elegans p38 MAP kinase pathway mutant protects from dopamine, 
      methamphetamine, and MDMA toxicity.
PG  - 99-103
LID - 10.1016/j.neulet.2011.04.071 [doi]
AB  - Biogenic amine systems are damaged by amphetamine abuse and in Parkinson's 
      disease. The mechanisms mediating this damage are of high importance because of 
      the public health impact of these problems. Here we have taken advantage of the 
      Caenorhabditis elegans nematode model system to investigate genetic modifiers of 
      biogenic amine toxicity. In a forward genetic screen, we identified a mutant 
      resistant to the toxic effects of dopamine. This mutant was also resistant to 
      toxic doses of methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA). 
      In addition, this mutation conferred resistance to 6-hydroxydopamine damage to 
      dopaminergic neurons in a Parkinson's disease model. Resistance was due to a 
      mutation in the nsy-1 gene, orthologous to the mammalian ASK-1 MAPKKK. NSY-1 is 
      in the highly conserved p38 MAP kinase pathway, which plays a crucial role in C. 
      elegans innate immunity, suggesting that this pathway may play a role in biogenic 
      amine toxicity system damage due to amphetamines and in the pathogenesis of 
      Parkinson's disease in higher organisms.
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - Schreiber, Matthew A
AU  - Schreiber MA
AD  - Ernest Gallo Clinic and Research Center, University of California, San Francisco, 
      5858 Horton Street Suite 200, Emeryville, CA 94608, United States. 
      matthewschreiber17@gmail.com
FAU - McIntire, Steven L
AU  - McIntire SL
LA  - eng
GR  - T32 MH019552-15/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110505
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Dopamine Agents)
RN  - 0 (Serotonin Agents)
RN  - 44RAL3456C (Methamphetamine)
RN  - EC 2.7.11.1 (NSY-1 protein, C elegans)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Caenorhabditis elegans/drug effects/*genetics
MH  - Caenorhabditis elegans Proteins/*genetics
MH  - Dopamine/*toxicity
MH  - Dopamine Agents/*toxicity
MH  - Immunity, Innate/*physiology
MH  - Methamphetamine/toxicity
MH  - Mutation
MH  - N-Methyl-3,4-methylenedioxyamphetamine/toxicity
MH  - Parkinson Disease/immunology/metabolism
MH  - Protein Serine-Threonine Kinases/*genetics
MH  - Serotonin Agents/*toxicity
MH  - Signal Transduction/*drug effects/genetics
MH  - p38 Mitogen-Activated Protein Kinases/genetics
PMC - PMC3119726
MID - NIHMS298975
EDAT- 2011/05/14 06:00
MHDA- 2011/11/08 06:00
PMCR- 2012/07/01
CRDT- 2011/05/14 06:00
PHST- 2011/01/07 00:00 [received]
PHST- 2011/04/27 00:00 [revised]
PHST- 2011/04/27 00:00 [accepted]
PHST- 2011/05/14 06:00 [entrez]
PHST- 2011/05/14 06:00 [pubmed]
PHST- 2011/11/08 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - S0304-3940(11)00555-6 [pii]
AID - 10.1016/j.neulet.2011.04.071 [doi]
PST - ppublish
SO  - Neurosci Lett. 2011 Jul 1;498(1):99-103. doi: 10.1016/j.neulet.2011.04.071. Epub 
      2011 May 5.