High-fat diet causes increased endogenous neurotoxins and phenotype of Parkinson’s disease in mice  

作　　者：Hanyan Wu Bingjie Xie Ming Ke Yulin Deng 

机构地区：[1]School of Life Science,Beijing Institute of Technology,Beijing 100081,China [2]Beijing Institute of Drug Control,Beijing 102206,China

出　　处：《Acta Biochimica et Biophysica Sinica》2019年第9期969-971,共3页生物化学与生物物理学报（英文版）

摘　　要：Clinical data showed that patients with type 2 diabetes(T2D)are more likely to develop Parkinson’s disease(PD)than normal people[1].Particularly when patients are in the early stage of T2D,their risk of PD is seven times higher than normal ones[2,3].However,the mechanism of how T2D induces PD risk is still not clear.Both genetic and environmental factors can contribute to dopamine(DA)neuron degeneration,which is an important pathological feature in PD development[4,5].In the aspect of environmental factor,1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP),an exogenous neurotoxin,has been found to have selective destruction effect on dopaminergic neurons of substantia nigra,and has been used as an effective reagent to construct PD models[6].Catechol tetrahydroisoquinolines(CAIQs)has been identified as an endogenous neurotoxin that has similar molecular structure to MPTP,such as salsolinol(Sal)and N-methyl-salsolinol(NM-Sal).It is possible that endogenous neurotoxin accumulation in brain may cause damage to dopaminergic neurons and impair their function.Abnormal glucose metabolism produces a large amount of reactive oxygen species,which could attack polyunsaturated fatty acids in biofilms,trigger lipid peroxidation,and produce large amounts of reactive aldehydes.The reactive aldehydes may react with DA by Pictet–Spengler reaction[7].Their synthetic products are the CAIQs.Furthermore,results from our lab showed that Sal and NM-Sal can cause mitochondrial damage in PC12 cells,a dopaminergic cell line,which eventually results in cell death[8,9].The purpose of this study was to investigate whether glucose intolerance induced by high-fat diet(HFD)in mice promotes endogenous neurotoxin accumulation to damage dopaminergic neurons in brain.

关 键 词：ENDOGENOUS metabolism PEROXIDATION 

分 类 号：R74[医药卫生—神经病学与精神病学]