Pasquali Livia, Lazzeri Gloria, Isidoro Ciro, Ruggieri Stefano, Paparelli Antonio, Fornai Francesco
Department of Neuroscience, Section of Neurology, University of Pisa, Pisa, Italy.
Ann N Y Acad Sci. 2008 Oct;1139:191-6. doi: 10.1196/annals.1432.016.
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.
甲基苯丙胺会导致黑质纹状体去神经支配和纹状体多巴胺丧失,同时保留黑质细胞体。黑质多巴胺神经元具有自噬泡以及胞质α-突触核蛋白、泛素和帕金蛋白阳性的包涵体样结构。基于此,自噬被认为在甲基苯丙胺诱导的神经毒性中至关重要,但其神经毒性或保护作用从未得到探讨。在此,我们回顾了关于自噬激活的描述性证据与对其在甲基苯丙胺中毒期间作用缺乏了解之间的差距。我们的初步研究结果排除了自噬的有害作用;这是理解自噬激活在甲基苯丙胺毒性中的后果的第一步。