Targeting autophagy using small-molecule compounds to improve potential therapy of Parkinson's disease

Kai Zhang1, Shiou Zhu1, Jiamei Li1

  • 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China.

Keywords:
3-MA, 3-methyladenine5-HT2A, Serotonin 2A5-HT2C, serotonin 2CA2A, adenosine 2AAADC, aromatic amino acid decarboxylaseALP, autophagy-lysosomal pathwayAMPK, 5ʹAMP-activated protein kinaseATG, autophagy related proteinATP13A2, ATPase cation transporting 13A2ATTEC, autophagosome-tethering compoundAUC, the area under the curveAUTAC, autophagy targeting chimeraAutophagyBAF, bafilomycinA1BBB, blood−brain barrierCL, clearance rateCMA, chaperone-mediated autophagyCNS, central nervous systemCOMT, catechol-O-methyltransferaseDA, dopamineDAT, dopamine transporterDJ-1, Parkinson protein 7DR, dopamine receptorER, endoplasmic reticulumERRα, estrogen-related receptor alphaF, oral bioavailabilityGAPDH, glyceraldehyde 3-phosphate dehydrogenaseGBA, glucocerebrosidase β acidGWAS, genome-wide association studyHDAC6, histone deacetylase 6HSC70, heat shock cognate 71 kDa proteinHSPA8, heat shock 70 kDa protein 8IMPase, inositol monophosphataseIPPase, inositol polyphosphate 1-phosphataseKI, knockinLAMP2A, lysosome-associated membrane protein 2 ALC3, light chain 3LIMP-2, lysosomal integrated membrane protein-2LRRK2, leucine-rich repeat sequence kinase 2LRS, leucyl-tRNA synthetaseLUHMES, lund human mesencephalicLamp2a, type 2A lysosomal-associated membrane proteinMAO-B, monoamine oxidase BMPP+, 1-methyl-4-phenylpyridiniumMPTP, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridineMYCBP2, MYC-binding protein 2NMDA, N-methyl-d-aspartic acidONRs, orphan nuclear receptorsPD therapyPD, Parkinson's diseasePDE4, phosphodiesterase 4PI3K, phosphatidylinositol 3-kinasePI3P, phosphatidylinositol 3-phosphatePINK1, PTEN-induced kinase 1PLC, phospholipase CPREP, prolyl oligopeptidaseParkin, parkin RBR E3 ubiquitin−protein ligaseParkinson's disease (PD)ROS, reactive oxygen speciesSAR, structure–activity relationshipSAS, solvent accessible surfaceSN, substantia nigraSNCA, α-synuclein geneSYT11, synaptotagmin 11Small-molecule compoundTFEB, transcription factor EBTSC2, tuberous sclerosis complex 2TargetULK1, UNC-51-like kinase 1UPS, ubiquitin−proteasome systemmAChR, muscarinic acetylcholine receptormTOR, the mammalian target of rapamycinα-syn, α-synuclein

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