Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease  

作　　者：Sandro Huenchuguala Juan Segura-Aguilar 

机构地区：[1]Escuela de Tecnología Médica,Facultad de Salud,Universidad Santo Tomás,Los Carreras,Osorno,Chile [2]Molecular&Clinical Pharmacology,Instituto de Ciencias Biomedicas(ICBM),Faculty of medicine,University of Chile,Independencia,Santiago,Chile

出　　处：《Neural Regeneration Research》2024年第3期529-535,共7页中国神经再生研究（英文版）

摘　　要：The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigr

关 键 词：1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine 6-HYDROXYDOPAMINE aminochrome dopaminergic neurons DT-diaphorase exogenous neurotoxins glutathione transferase M2-2 

分 类 号：R742.5[医药卫生—神经病学与精神病学]