Pathways of methamphetamine toxicity.
Methamphetamine (METH) is a drug of abuse which is neurotoxic for the nigrostriatal system. METH-induced neurodegeneration involves production of reactive oxygen species, triggering autophagic vacuoles within nigral neurons of chronic abusers of METH. In fact, Cu,Zn-superoxide dismutase 1 (SOD1) is a critical protein for the neurotoxic effects of METH on DA neurons. Moreover, mutations in the SOD1 gene cause amyotrophic lateral sclerosis, a dramatic neurodegenerative disorder. In the present paper we demonstrate that in G93A transgenic mice, overexpressing the ALS-linked mutant form of SOD1, surviving motor neurons share common intracellular alterations with METH-exposed DA neurons. We hypothesize that in mutant SOD1 transgenic mice, a defective autophagy might be responsible for the neurotoxic effects seen with in nigral neurons during METH toxicity.
Ferrucci
Michela
M
Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.
Pasquali
Livia
L
Paparelli
Antonio
A
Ruggieri
Stefano
S
Fornai
Francesco
F
D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity*; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D025801:Ubiquitin / Q000378:metabolism
D015259:Dopamine Agents; C000606290:SOD1 protein, human; D025801:Ubiquitin; D008694:Methamphetamine; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D004298:Dopamine