中文
Earlier issues
Announcement
More
Progress in Chemistry 2020, Vol. 32 Issue (1): 14-22 DOI: 10.7536/PC191212 Previous Articles   Next Articles

Truncated and Modified Aβ Species in Alzheimer’s Disease

Gao Li1,**(), Yan-Mei Li2,3,4,**()   

  1. 1. Institute of Oceanography, Minjiang University, Fuzhou 350108, China
    2. Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China
    3. Beijing Institute for Brain Disorders, Beijing 100069, China
    4. Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China
  • Received: Online: Published:
  • Contact: Gao Li, Yan-Mei Li
  • About author:
    ** E-mail: (Gao Li);
    (Yan-Mei Li)
  • Supported by:
    National Key Research and Development Program of China(2018YFA0507600); National Natural Science Foundation of China(81661148047); Talent Introduction Fund of Minjiang University(MJY19025)
Richhtml ( 24 ) PDF ( 394 ) Cited
Export

EndNote

Ris

BibTeX

Aggregation of β-amyloid (Aβ) has been considered as an important factor leading to Alzheimer’s disease (AD). Previous studies have focused on the full-length unmodified Aβ1-40 and Aβ1-42. In recent years, it was found that a variety of truncated and modified Aβ species co-exist in AD patients’ brain. These Aβ species contributed to the progression of AD and should not be overlooked. For example, the emergence of pyroglutamated Aβ and phosphorylated Aβ is considered as symptoms of AD. And the most abundant Aβ species in AD patients’ brain should be Aβ4-40/42, which has similar aggregation properties and toxicity with Aβ1-40/42. Due to the elevated oxidative stress in AD patients’ brain, tyrosine nitration, dimerization and methionine oxidation were also identified in Aβ sequence, resulting in different properties. We review here the production, structure and toxicity of different Aβ species and summarize their possible roles in AD pathology.

Key words: β-amyloid;, Alzheimer’s disease;, truncation, phosphorylation, pyroglutamylation
Fig. 1 Sequence of Aβ and the sites for truncation or modification[13]
Fig. 2 Prophylactic vaccine based on pyroglutamate-3 Aβ[33]. Copyright 2016 American Chemical Society
Fig. 3 Toxicity of different truncated and modified Aβ, tested on primary neurons[35]
Fig. 4 Possible binding mode between FRH sequence and Cu2+
Fig. 5 Phosphorylation at 26-Ser could disturb the salt bridge between D23 and K28[45]. Copyright 2014 American Chemical Society
Fig. 6 The aggregation and toxicity of synthetic Aβ42 [57]
Fig. 7 Crystal structure of isoAsp23-Aβ20-34 fibril[78]
[1]
Skovronsky D M , Lee V M Y , Trojanowskiz J Q . Annu. Rev. Pathol.: Mech. Dis., 2006,1:151. https://www.ncbi.nlm.nih.gov/pubmed/18039111

doi: 10.1146/annurev.pathol.1.110304.100113 pmid: 18039111
[2]
World Alzheimer Report 2018. The state of the art of dementia research: New frontiers; Report 2018. The state of the art of dementia research: New frontiers; Alzheimer’s Disease International: London, 2018.
[3]
Goedert M , Spillantini M G . Science, 2006,314:777. https://www.ncbi.nlm.nih.gov/pubmed/17082447

doi: 10.1126/science.1132814 pmid: 17082447
[4]
Hardy J A , Higgins G A . Science, 1992,256:184. https://www.ncbi.nlm.nih.gov/pubmed/1566067

doi: 10.1126/science.1566067 pmid: 1566067
[5]
Blennow K , Hampel H , Weiner M , Zetterberg H . Nat. Rev. Neurol., 2010,6:131. https://www.ncbi.nlm.nih.gov/pubmed/20157306

doi: 10.1038/nrneurol.2010.4 pmid: 20157306
[6]
Selkoe D J , Hardy J . EMBO Mol. Med., 2016,8:595. https://www.ncbi.nlm.nih.gov/pubmed/27025652

doi: 10.15252/emmm.201606210 pmid: 27025652
[7]
Musiek E S , Holtzman D M . Nat. Neurosci., 2015,18:800. https://www.ncbi.nlm.nih.gov/pubmed/26007213

doi: 10.1038/nn.4018 pmid: 26007213
[8]
Hamley I W . Chem. Rev., 2012,112:5147. https://www.ncbi.nlm.nih.gov/pubmed/22813427

doi: 10.1021/cr3000994 pmid: 22813427
[9]
Chen G F , Xu T H , Yan Y , Zhou Y R , Jiang Y , Melcher K , Xu H E . Acta Pharmacol.Sin., 2017,38:1205.
[10]
[2019-12-10] https://www.alzforum.org/therapeutics/. https://www.alzforum.org/therapeutics/
[11]
[2019-12-10] . https://clinicaltrials.gov/
[12]
Zhao D S , Chen Y X , Liu Q , Zhao Y F , Li Y M . Sci. China: Chem., 2012,55:112. http://link.springer.com/10.1007/s11426-011-4451-3

doi: 10.1007/s11426-011-4451-3
[13]
Kummer M P , Heneka M T . Alzheimer’s Res. Ther., 2014,6:28.
[14]
Miles L A , Crespi G A , Doughty L , Parker M W . Sci. Rep., 2013,3:1302. https://www.ncbi.nlm.nih.gov/pubmed/23416764

doi: 10.1038/srep01302 pmid: 23416764
[15]
Bouter Y Lopez Noguerola J S , Tucholla P , Crespi G A , Parker M W , Wiltfang J , Miles L A , Bayer T A . Acta Neuropathol., 2015,130:713. https://www.ncbi.nlm.nih.gov/pubmed/26467270

doi: 10.1007/s00401-015-1489-x pmid: 26467270
[16]
Vassar R , Bennett B D , Babu-Khan S , Kahn S , Mendiaz E A , Denis P , Teplow D B , Ross S , Amarante P , Loeloff R , Luo Y , Fisher S , Fuller J , Edenson S , Lile J , Jarosinski M A , Biere A L , Curran E , Burgess T , Louis J C , Collins F , Treanor J , Rogers G , Citron M . Science, 1999,286:735. https://www.ncbi.nlm.nih.gov/pubmed/10531052

doi: 10.1126/science.286.5440.735 pmid: 10531052
[17]
Liu K , Solano I , Mann D , Lemere C , Mercken M , Trojanowski J Q , Lee V M . Acta Neuropathol., 2006,112:163.
[18]
Mori H , Takio K , Ogawara M , Selkoe D . J. Biol. Chem., 1992,267:17082. https://www.ncbi.nlm.nih.gov/pubmed/1512246

pmid: 1512246
[19]
Portelius E , Bogdanovic N , Gustavsson M K , Volkmann I , Brinkmalm G , Zetterberg H , Winblad B , Blennow K . Acta Neuropathol., 2010,120:185. https://www.ncbi.nlm.nih.gov/pubmed/20419305

doi: 10.1007/s00401-010-0690-1 pmid: 20419305
[20]
Lewis H , Beher D , Cookson N , Oakley A , Piggott M , Morris C M , Jaros E , Perry R , Ince P , Kenny R A , Ballard C G , Shearman M S , Kalaria R N . Neuropathol. Appl. Neurobiol., 2006,32:103. https://www.ncbi.nlm.nih.gov/pubmed/16599940

doi: 10.1111/j.1365-2990.2006.00696.x pmid: 16599940
[21]
Sevalle J , Amoyel A , Robert P , Fournie-Zaluski M C , Roques B , Checler F . J. Neurochem., 2009,109:248. https://www.ncbi.nlm.nih.gov/pubmed/19187443

doi: 10.1111/j.1471-4159.2009.05950.x pmid: 19187443
[22]
Schilling S , Hoffmann T , Manhart S , Hoffmann M , Demuth H U . FEBS Lett., 2004,563:191. https://www.ncbi.nlm.nih.gov/pubmed/15063747

doi: 10.1016/S0014-5793(04)00300-X pmid: 15063747
[23]
Russo C , Violani E , Salis S , Venezia V , Dolcini V , Damonte G , Benatti U , D’Arrigo C , Patrone E , Carlo P , Schettini G . J. Neurochem., 2002,82:1480. https://www.ncbi.nlm.nih.gov/pubmed/12354296

doi: 10.1046/j.1471-4159.2002.01107.x pmid: 12354296
[24]
Nussbaum J M , Schilling S , Cynis H , Silva A , Swanson E , Wangsanut T , Tayler K , Wiltgen B , Hatami A , Ronicke R , Reymann K , Hutter-Paier B , Alexandru A , Jagla W , Graubner S , Glabe C G , Demuth H U , Bloom G S . Nature, 2012,485:651. https://www.ncbi.nlm.nih.gov/pubmed/22660329

doi: 10.1038/nature11060 pmid: 22660329
[25]
Wulff M , Baumann M , Thummler A , Yadav J K , Heinrich L , Knupfer U , Schlenzig D , Schierhorn A , Rahfeld J U , Horn U , Balbach J , Demuth H U , Fändrich M . Angew. Chem. Int. Ed., 2016,55:5081. https://www.ncbi.nlm.nih.gov/pubmed/26970534

doi: 10.1002/anie.201511099 pmid: 26970534
[26]
Schilling S , Zeitschel U , Hoffmann T , Heiser U , Francke M , Kehlen A , Holzer M , Hutter-Paier B , Prokesch M , Windisch M , Jagla W , Schlenzig D , Lindner C , Rudolph T , Reuter G , Cynis H , Montag D , Demuth H U , Rossner S . Nat. Med., 2008,14:1106. https://www.ncbi.nlm.nih.gov/pubmed/18836460

doi: 10.1038/nm.1872 pmid: 18836460
[27]
Rijal Upadhaya A , Kosterin I , Kumar S , von Arnim C A , Yamaguchi H , Fandrich M , Walter J , Thal D R . Brain, 2014,137:887. https://www.ncbi.nlm.nih.gov/pubmed/24519982

doi: 10.1093/brain/awt362 pmid: 24519982
[28]
Wirths O , Erck C , Martens H , Harmeier A , Geumann C , Jawhar S , Kumar S , Multhaup G , Walter J , Ingelsson M , Degerman-Gunnarsson M , Kalimo H , Huitinga I , Lannfelt L , Bayer T A . J. Biol. Chem., 2010,285:41517. https://www.ncbi.nlm.nih.gov/pubmed/20971852

doi: 10.1074/jbc.M110.178707 pmid: 20971852
[29]
Frost J L , Liu B , Kleinschmidt M , Schilling S , Demuth H U , Lemere C A . Neurodegener. Dis., 2012,10:265. https://www.ncbi.nlm.nih.gov/pubmed/22343072

doi: 10.1159/000335913 pmid: 22343072
[30]
Demattos R B , Lu J , Tang Y , Racke M M , Delong C A , Tzaferis J A , Hole J T , Forster B M , McDonnell P C , Liu F , Kinley R D , Jordan W H , Hutton M L . Neuron, 2012,76:908. https://www.ncbi.nlm.nih.gov/pubmed/23217740

doi: 10.1016/j.neuron.2012.10.029 pmid: 23217740
[31]
Acero G , Manoutcharian K , Vasilevko V , Munguia M E , Govezensky T , Coronas G , Luz-Madrigal A , Cribbs D H , Gevorkian G . J. Neuroimmunol., 2009,213:39. https://www.ncbi.nlm.nih.gov/pubmed/19545911

doi: 10.1016/j.jneuroim.2009.06.003 pmid: 19545911
[32]
Perez-Garmendia R , Ibarra-Bracamontes V , Vasilevko V , Luna-Munoz J , Mena R , Govezensky T , Acero G , Manoutcharian K , Cribbs D H , Gevorkian G . J. Neuroimmunol., 2010,229:248. https://www.ncbi.nlm.nih.gov/pubmed/20864186

doi: 10.1016/j.jneuroim.2010.08.020 pmid: 20864186
[33]
Li G , Hu Z W , Chen P G , Sun Z Y , Chen Y X , Zhao Y F , Li Y M . ACS Chem. Neurosci., 2017,8:454. https://www.ncbi.nlm.nih.gov/pubmed/28292186

doi: 10.1021/acschemneuro.6b00336 pmid: 28292186
[34]
Masters C L , Simms G , Weinman N A , Multhaup G , McDonald B L , Beyreuther K . Proc. Natl. Acad. Sci. U.S.A., 1985,82:4245. https://www.ncbi.nlm.nih.gov/pubmed/3159021

doi: 10.1073/pnas.82.12.4245 pmid: 3159021
[35]
Bouter Y , Dietrich K , Wittnam J L , Rezaei-Ghaleh N , Pillot T , Papot-Couturier S , Lefebvre T , Sprenger F , Wirths O , Zweckstetter M , Bayer T A . Acta Neuropathol., 2013,126:189. https://www.ncbi.nlm.nih.gov/pubmed/23685882

doi: 10.1007/s00401-013-1129-2 pmid: 23685882
[36]
Li G , Yang W Y , Zhao Y F , Chen Y X , Hong L , Li Y M . Chem. Eur. J., 2018,24:13647. https://www.ncbi.nlm.nih.gov/pubmed/29901238

doi: 10.1002/chem.201802655 pmid: 29901238
[37]
Antonios G , Saiepour N , Bouter Y , Richard B C , Paetau A , Verkkoniemi-Ahola A , Lannfelt L , Ingelsson M , Kovacs G G , Pillot T , Wirths O , Bayer T A . Acta Neuropathol. Commun., 2013,1:56. https://www.ncbi.nlm.nih.gov/pubmed/24252153

doi: 10.1186/2051-5960-1-56 pmid: 24252153
[38]
Antonios G , Borgers H , Richard B C , Brauss A , Meissner J , Weggen S , Pena V , Pillot T , Davies S L , Bakrania P , Matthews D , Brownlees J , Bouter Y , Bayer T A . Sci. Rep., 2015,5:17338. https://www.ncbi.nlm.nih.gov/pubmed/26626428

doi: 10.1038/srep17338 pmid: 26626428
[39]
Mital M , Wezynfeld N E , Fraczyk T , Wiloch M Z , Wawrzyniak U E , Bonna A , Tumpach C , Barnham K J , Haigh C L , Bal W , Drew S C . Angew. Chem. Int. Ed., 2015,54:10460. https://www.ncbi.nlm.nih.gov/pubmed/26178596

doi: 10.1002/anie.201502644 pmid: 26178596
[40]
Wezynfeld N E , Stefaniak E , Stachucy K , Drozd A , Plonka D , Drew S C , Krezel A , Bal W . Angew. Chem. Int. Ed., 2016,55:8235. https://www.ncbi.nlm.nih.gov/pubmed/27238224

doi: 10.1002/anie.201511968 pmid: 27238224
[41]
Barritt J D , Viles J H . J. Biol. Chem., 2015,290:27791. https://www.ncbi.nlm.nih.gov/pubmed/26408196

doi: 10.1074/jbc.M115.684084 pmid: 26408196
[42]
Naslund J , Schierhorn A , Hellman U , Lannfelt L , Roses A D , Tjernberg L O , Silberring J , Gandy S E , Winblad B , Greengard P . Proc. Natl. Acad. Sci. U.S.A, 1994,91:8378. https://www.ncbi.nlm.nih.gov/pubmed/8078890

doi: 10.1073/pnas.91.18.8378 pmid: 8078890
[43]
Milton N G N . Neuroreport 2001,12:3839. https://www.ncbi.nlm.nih.gov/pubmed/11726805

doi: 10.1097/00001756-200112040-00047 pmid: 11726805
[44]
Kumar S , Rezaei-Ghaleh N , Terwel D , Thal D R , Richard M , Hoch M , Mc Donald J M , Wullner U , Glebov K , Heneka M T , Walsh D M , Zweckstetter M , Walter J . EMBO J., 2011,30:2255. https://www.ncbi.nlm.nih.gov/pubmed/21527912

doi: 10.1038/emboj.2011.138 pmid: 21527912
[45]
Rezaei-Ghaleh N , Amininasab M , Giller K , Kumar S , Stundl A , Schneider A , Becker S , Walter J , Zweckstetter M . J. Am. Chem. Soc., 2014,136:4913. https://www.ncbi.nlm.nih.gov/pubmed/24617810

doi: 10.1021/ja411707y pmid: 24617810
[46]
Kumar S , Wirths O , Stuber K , Wunderlich P , Koch P , Theil S , Rezaei-Ghaleh N , Zweckstetter M , Bayer T A , Brustle O , Thal D R , Walter J . Acta Neuropathol., 2016,131:525. https://www.ncbi.nlm.nih.gov/pubmed/26898910

doi: 10.1007/s00401-016-1546-0 pmid: 26898910
[47]
Hu Z W , Ma M R , Chen Y X , Zhao Y F , Qiang W , Li Y M . J. Biol. Chem., 2017,292:2611. https://www.ncbi.nlm.nih.gov/pubmed/28031462

doi: 10.1074/jbc.M116.757179 pmid: 28031462
[48]
Kumar S , Singh S , Hinze D , Josten M , Sahl H G , Siepmann M , Walter J . J. Biol. Chem., 2012,287:8641. https://www.ncbi.nlm.nih.gov/pubmed/22267728

doi: 10.1074/jbc.M111.279133 pmid: 22267728
[49]
Rezaei-Ghaleh N , Amininasab M , Kumar S , Walter J , Zweckstetter M . Nat. Commun., 2016,7:11359. https://www.ncbi.nlm.nih.gov/pubmed/27072999

doi: 10.1038/ncomms11359 pmid: 27072999
[50]
Hu Z W , Vugmeyster L , Au D F , Ostrovsky D , Sun Y , Qiang W . Proc. Natl. Acad. Sci. U.S.A., 2019,116:11253. https://www.ncbi.nlm.nih.gov/pubmed/31097588

doi: 10.1073/pnas.1818530116 pmid: 31097588
[51]
Xiao Y , Ma B , McElheny D , Parthasarathy S , Long F , Hoshi M , Nussinov R , Ishii Y . Nat. Struct. Mol. Biol., 2015,22:499. https://www.ncbi.nlm.nih.gov/pubmed/25938662

doi: 10.1038/nsmb.2991 pmid: 25938662
[52]
Radi R . Proc. Natl. Acad. Sci. U.S.A., 2004,101:4003. https://www.ncbi.nlm.nih.gov/pubmed/15020765

doi: 10.1073/pnas.0307446101 pmid: 15020765
[53]
Burai R , Ait-Bouziad N , Chiki A , Lashuel H A . J. Am. Chem. Soc., 2015,137:5041. https://www.ncbi.nlm.nih.gov/pubmed/25768729

doi: 10.1021/ja5131726 pmid: 25768729
[54]
Fernandez-Vizarra P , Fernandez A P , Castro-Blanco S , Encinas J M , Serrano J , Bentura M L , Munoz P , Martinez-Murillo R , Rodrigo J . Neurobiol. Dis., 2004,15:287. c98fc8a5-c07d-4571-a1e9-38b990ac453d http://www.sciencedirect.com/science/article/pii/S0969996103002109

doi: 10.1016/j.nbd.2003.10.010
[55]
Kummer M P , Hermes M , Delekarte A , Hammerschmidt T , Kumar S , Terwel D , Walter J , Pape H C , Konig S , Roeber S , Jessen F , Klockgether T , Korte M , Heneka M T . Neuron, 2011,71:833. ed22fa90-adb9-4ad0-9b6a-44165036a5e2 http://www.sciencedirect.com/science/article/pii/S0896627311005952

doi: 10.1016/j.neuron.2011.07.001
[56]
Zhao J , Wang P , Li H , Gao Z . Chem. Res. Toxicol., 2015,28:401. https://www.ncbi.nlm.nih.gov/pubmed/25387246

doi: 10.1021/tx500353s pmid: 25387246
[57]
Guivernau B , Bonet J , Valls-Comamala V , Bosch-Morato M , Godoy J A , Inestrosa N C , Peralvarez-Marin A , Fernandez-Busquets X , Andreu D , Oliva B , Munoz F J . J. Neurosci., 2016,36:11693. https://www.ncbi.nlm.nih.gov/pubmed/27852777

doi: 10.1523/JNEUROSCI.1081-16.2016 pmid: 27852777
[58]
Galeazzi L , Ronchi P , Franceschi C , Giunta S . Amyloid: the International Journal of Experimental and Clinical Investigation: the Official Journal of the International Society of Amyloidosis, 1999,6:7. http://www.tandfonline.com/doi/full/10.3109/13506129908993282

doi: 10.3109/13506129908993282
[59]
Atwood C S , Perry G , Zeng H , Kato Y , Jones W D , Ling K Q , Huang X , Moir R D , Wang D , Sayre L M , Smith M A , Chen S G , Bush A I . Biochemistry, 2004,43:560. https://www.ncbi.nlm.nih.gov/pubmed/14717612

doi: 10.1021/bi0358824 pmid: 14717612
[60]
Al-Hilaly Y K , Williams T L , Stewart-Parker M , Ford L , Skaria E , Cole M , Bucher W G , Morris K L , Sada A A , Thorpe J R , Serpell L C . Acta Neuropathol. Commun., 2013,1:83. https://www.ncbi.nlm.nih.gov/pubmed/24351276

doi: 10.1186/2051-5960-1-83 pmid: 24351276
[61]
Brinkmalm G , Hong W , Wang Z , Liu W , O’Malley T T , Sun X , Frosch M P , Selkoe D J , Portelius E , Zetterberg H , Blennow K , Walsh D M . Brain, 2019,142:1441. https://www.ncbi.nlm.nih.gov/pubmed/31032851

doi: 10.1093/brain/awz066 pmid: 31032851
[62]
Vazquez de la Torre A , Gay M , Vilaprinyo-Pascual S , Mazzucato R , Serra-Batiste M , Vilaseca M , Carulla N . Anal. Chem., 2018,90:4552. https://www.ncbi.nlm.nih.gov/pubmed/29537826

doi: 10.1021/acs.analchem.7b04936 pmid: 29537826
[63]
Kok W M , Cottam J M , Ciccotosto G D , Miles L A , Karas J A , Scanlon D B , Roberts B R , Parker M W , Cappai R , Barnham K J , Hutton C A . Chem. Sci., 2013,4:4449. http://xlink.rsc.org/?DOI=c3sc22295k

doi: 10.1039/c3sc22295k
[64]
Varadarajan S , Kanski J , Aksenova M , Lauderback C , Butterfield D A . J. Am. Chem. Soc., 2001,123:5625. https://www.ncbi.nlm.nih.gov/pubmed/11403592

doi: 10.1021/ja010452r pmid: 11403592
[65]
Hou L , Kang I , Marchant R E , Zagorski M G . J. Biol. Chem., 2002,277:40173. https://www.ncbi.nlm.nih.gov/pubmed/12198111

doi: 10.1074/jbc.C200338200 pmid: 12198111
[66]
Palmblad M , Westlind-Danielsson A , Bergquist J . J. Biol. Chem., 2002,277:19506. https://www.ncbi.nlm.nih.gov/pubmed/11912198

doi: 10.1074/jbc.M112218200 pmid: 11912198
[67]
Barnham K J , Ciccotosto G D , Tickler A K , Ali F E , Smith D G , Williamson N A , Lam Y H , Carrington D , Tew D , Kocak G , Volitakis I , Separovic F , Barrow C J , Wade J D , Masters C L , Cherny R A , Curtain C C , Bush A I , Cappai R . J. Biol. Chem., 2003,278:42959. https://www.ncbi.nlm.nih.gov/pubmed/12925530

doi: 10.1074/jbc.M305494200 pmid: 12925530
[68]
Hou L , Shao H , Zhang Y , Li H , Menon N K , Neuhaus E B , Brewer J M , Byeon I J , Ray D G , Vitek M P , Iwashita T , Makula R A , Przybyla A B , Zagorski M G . J. Am. Chem. Soc., 2004,126:1992. https://www.ncbi.nlm.nih.gov/pubmed/14971932

doi: 10.1021/ja036813f pmid: 14971932
[69]
Razzokov J , Yusupov M , Bogaerts A . Sci. Rep., 2019,9:5476. https://www.ncbi.nlm.nih.gov/pubmed/30940901

doi: 10.1038/s41598-019-41931-6 pmid: 30940901
[70]
Brown A M , Lemkul J A , Schaum N , Bevan D R . Arch. Biochem. Biophys., 2014,545:44. https://www.ncbi.nlm.nih.gov/pubmed/24418316

doi: 10.1016/j.abb.2014.01.002 pmid: 24418316
[71]
Perdivara I , Petrovich R , Allinquant B , Deterding L J , Tomer K B , Przybylski M . Journal of Proteome Research, 2009,8:631. https://www.ncbi.nlm.nih.gov/pubmed/19093876

doi: 10.1021/pr800758g pmid: 19093876
[72]
Halim A , Brinkmalm G , Ruetschi U , Westman-Brinkmalm A , Portelius E , Zetterberg H , Blennow K , Larson G , Nilsson J . Proc. Natl. Acad. Sci. U.S.A., 2011,108:11848. https://www.ncbi.nlm.nih.gov/pubmed/21712440

doi: 10.1073/pnas.1102664108 pmid: 21712440
[73]
Wang P , Nilsson J , Brinkmalm G , Larson G , Huang X F . Chem. Commun., 2014,50:15067. https://www.ncbi.nlm.nih.gov/pubmed/25329175

doi: 10.1039/c4cc05085a pmid: 25329175
[74]
Nilsson J , Brinkmalm G , Ramadan S , Gilborne L , Noborn F , Blennow K , Wallin A , Svensson J , Abo-Riya M A , Huang X , Larson G . Sci. Rep., 2019,9:5522. https://www.ncbi.nlm.nih.gov/pubmed/30940835

doi: 10.1038/s41598-019-41897-5 pmid: 30940835
[75]
Shimizu T , Watanabe A , Ogawara M , Mori H , Shirasawa T . Arch. Biochem. Biophys., 2000,381:225. https://www.ncbi.nlm.nih.gov/pubmed/11032409

doi: 10.1006/abbi.2000.1955 pmid: 11032409
[76]
Fukuda H , Shimizu T , Nakajima M , Mori H , Shirasawa T . Bioorg. Med. Chem. Lett., 1999,9:953. https://www.ncbi.nlm.nih.gov/pubmed/10230618

doi: 10.1016/s0960-894x(99)00121-3 pmid: 10230618
[77]
Tomidokoro Y , Rostagno A , Neubert T A , Lu Y , Rebeck G W , Frangione B , Greenberg S M , Ghiso J . The American Journal of Pathology, 2010,176:1841. https://www.ncbi.nlm.nih.gov/pubmed/20228223

doi: 10.2353/ajpath.2010.090636 pmid: 20228223
[78]
Warmack R A , Boyer D R , Zee C T , Richards L S , Sawaya M R , Cascio D , Gonen T , Eisenberg D S , Clarke S G . Nat. Commun., 2019,10:3357. https://www.ncbi.nlm.nih.gov/pubmed/31350392

doi: 10.1038/s41467-019-11183-z pmid: 31350392
[79]
Kubo T , Kumagae Y , Miller C A , Kaneko I . J. Neuropathol. Exp. Neurol., 2003,62:248. https://www.ncbi.nlm.nih.gov/pubmed/12638729

doi: 10.1093/jnen/62.3.248 pmid: 12638729
[80]
Inoue K , Hosaka D , Mochizuki N , Akatsu H , Tsutsumiuchi K , Hashizume Y , Matsukawa N , Yamamoto T , Toyo’oka T . Anal. Chem, 2014,86:797. https://www.ncbi.nlm.nih.gov/pubmed/24283798

doi: 10.1021/ac403315h pmid: 24283798
[81]
Kaneko I , Morimoto K , Kubo T . Neuroscience, 2001,104:1003. https://www.ncbi.nlm.nih.gov/pubmed/11457586

doi: 10.1016/s0306-4522(01)00155-5 pmid: 11457586
[82]
Lambeth T R , Riggs D L , Talbert L E , Tang J , Coburn E , Kang A S , Noll J , Augello C , Ford B D , Julian R R . ACS Central Science, 2019,5:1387. https://www.ncbi.nlm.nih.gov/pubmed/31482121

doi: 10.1021/acscentsci.9b00369 pmid: 31482121
[1] Zhihua Gong, Sha Hu, Xueping Jin, Lei Yu, Yuanyuan Zhu, Shuangxi Gu. Synthetic Methods and Application of Phosphoester Prodrugs [J]. Progress in Chemistry, 2022, 34(9): 1972-1981.
[2] Gao Feifei, Wang Yuebo. Electrochemical Detection of Protein Phosphorylation [J]. Progress in Chemistry, 2014, 26(05): 856-865.
[3] Hao Yan,Fengchao Jiang*. Recent Advances in the Research of γ-Secretase Inhibitors [J]. Progress in Chemistry, 2006, 18(0203): 355-361.