Role of autophagy during methamphetamine neurotoxicity.
Methamphetamine causes nigrostriatal denervation and striatal dopamine loss, while sparing nigral cell bodies. Nigral dopamine neurons feature autophagic vacuoles and cytoplasmic alpha-synuclein-, ubiquitin- and parkin-positive inclusion-like bodies. On that basis, autophagy was considered essential in methamphetamine-induced neurotoxicity, but its neurotoxic or protective role has never been addressed. Here we review the gap between the descriptive evidence on activation of autophagy and the lack of knowledge about its role during methamphetamine intoxication. Our preliminary findings rule out a detrimental role for autophagy; this represents the first step in understanding the consequence of activation of autophagy in methamphetamine toxicity.
Pasquali
Livia
L
Department of Neuroscience, Section of Neurology, University of Pisa, Pisa, Italy.
Lazzeri
Gloria
G
Isidoro
Ciro
C
Ruggieri
Stefano
S
Paparelli
Antonio
A
Fornai
Francesco
F
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity*; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity*; D009410:Nerve Degeneration / Q000139:chemically induced; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D015259:Dopamine Agents; D008694:Methamphetamine; D004298:Dopamine