References
- Graham WV , Bonito-OlivaA , SakmarTP. Update on Alzheimer's disease therapy and prevention strategies. Annu. Rev. Med.68, 413–430 (2017).
- Kumar A , NishaCM , SilakariCet al. Current and novel therapeutic molecules and targets in Alzheimer's disease. J. Form. Med. Assoc.115, 3–10 (2016).
- Hara Y , McKeehanN , FillitHM. Translating the biology of aging into novel therapeutics for Alzheimer disease. Neurology92, 84–93 (2019).
- Winblad B , AmouyelP , AndrieuSet al. Defeating Alzheimer's disease and other dementias: a priority for European science and society. Lancet Neurol.15, 455–532 (2016).
- Coman H , NemesB. New therapeutic targets in Alzheimer's disease. Int. J. Gerontol.11, 2–6 (2017).
- Winblad B , PoritisN. Memantine in severe dementia. Results of the 9M-Best Study (benefit and efficacy in severely demented patients during treatment with memantine). Int. J. Geriatr. Psychiatry14, 137–146 (1999).
- Pereira AC , LambertH , GrossmannYSet al. Glutamatergic regulation prevents hippocampal-dependent age-related cognititive decline through dendritic spine clustering. PNAS111, 18733–18738 (2014).
- Linse S , ScheidtT , BernfurKet al. Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies. Nat. Struct. Mol. Biol.27, 1125–1133 (2020).
- Knopman DS , PerlmutterJS. Prescribing aducanumab in the face of meager efficacy and real risks. Neurology97, 545–547 (2021). doi: 10.1212/WNL.0000000000012452.
- Castellani RJ , Plascencia-VillaG , PerryG. The amyloid cascade and Alzheimer's disease therapeutics: theory versus observation. Laboratory Invest. doi: 10.1038/s41374-019-0231-z (2019).
- Kametani F , HasegawaM. Reconsideration of amyloid hypthesis and Tau hypothesis in Alzheimer's disease. Frontiers Neurosci.12, 25 (2018).
- Cummings J , LeeG , NahedPet al. Alzheimer's disease drug development pipeline: 2022 Alzheimers Dement 8, e12295 (2022).
- Doody RS , RamanR , FarlowMet al. A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N. Engl. J. Med.369, 341–350 (2013).
- Vossel KA , XuJC , FomenkoVet al. Tau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β. J Cell Biol.209, 419–433 (2015).
- Arendt T , StielerJT , HolzerM. Tau and tauopathies. Brain Res Bull.126, 238–292 (2016).
- Montoliu-Gaya L , VillegasS. Protein structures in Alzheimer's disease: the basis for rational therapeutic design. Arch. Biochem. Biophys.588, 1–14 (2015).
- Martin L , LatypovaX , WilsonCMet al. Tau protein kinase: involvement in Alzheimer's disease. Ageing Res. Rev.12, 289–309 (2013).
- Arif M , WeiJ , ZhangQet al. Cytoplasmic retention of protein phosphatase 2A inhibitor 2 (I2PP2A) induces Alzheimer-like abnormal hyperphosphorylation of Tau. J. Biol. Chem.289, 27677–27691 (2014).
- Liu F , Grundke-IqbalI , IqbalK , GongC-X. Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. Eur. J. Neurosci.22, 1942–1950 (2005).
- Sontag JM , SontagE. Protein phosphatase 2A dysfunction in Alzheimer's disease. Front Mol. Neurosci.7, 16 (2014).
- Maqbool M , MobashirM , HodaN. Pivotal role of glycogen synthase-3: a therapeutic target for Alzheimer's disease. Eur. J. Med. Chem.107, 63–81 (2016).
- Leclerc S , GarnierM , HoesselRet al. Indirubins inhibit glycogen synthase kinase-3β and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors? J. Biol. Chem. 276, 251–260 (2001).
- Coghlan MP , CulbertAA , CrossDAet al. Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem. Biol.7, 793–803 (2007).
- Bhat R , XueY , BergSet al. Structural insights and biological effects of glycogen synthase kinase specific inhibitor AR-A014418. J. Biol. Chem.278, 45937–45945 (2003).
- Eldar-Finkelman H , MartinezA. GSK3-inhibitors: preclinical and clinical focus on CNS. Front. Mol. Neurosci.4, 32 (2011).
- Lovestone S , BoadaM , DuboisBet al. A phase II trial of tideglusib in Alzheimer's disease. J. Alzheimer's Dis.1, 75–88 (2015).
- Cuny GD , UlyanovaNP , PatnailDet al. Structure-activity relationship study of beta-carboline derivatives as haspin kinase inhibitors. Bioorg. Med. Chem. Letters22, 2015–2019 (2012).
- Holzer M , SchadeN , OpitzAet al. Molecules 23, 2335 (2018).
- Hilgeroth A , KunaK , KuckländerU. Novel Functionalized 1,4,4a,9a-Tetrahydro-1-aza-9-oxafluorenes by Cycloaddition of 4-(4-Methoxyphenyl)-1,4-dihydropyridines and p-Benzoquinone. J. Heterocyclic Chem.25, 551–553 (1998).
- Comins DL , SmithRK , StroudED. Heterocycles22, 339–344 (1984).
- Wang J , WolfRM , CaldwellJW , KollmannPA , CaseDA. Development and testing of a general amber force field. J. Comput. Chem.25, 1157–1174 (2004).
- Jakalian A , JackDB , BaylyCI. Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation. J. Comput. Chem.23, 1623–1641 (2002).
- Jones G , WillettP , GlenRC , LeachAR , TylorR. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol.267, 727–748 (1997).
- Kramer T , SchmidtB , LeMonte F. Small-molecule inhibitors of GSK-3β: structural insights and their application to Alzheimer's disease models. Int. J. Alzheimer's Dis.381029 (2012).
- Counts SE , MufsonEJ. Regulator of cell cycle (RGCC) expression during the progression of Alzheimer's disease. Cell Transplant26, 693–702 (2017).
- Bhaskar K , HobbsGA , YenSH , LeeG. Tyrosine phosphorylation of tau accompanies disease progression in transgenic mouse models of tauopathy. Neuropathol. Appl. Neurobiol.36, 462–477 (2010).
- Arendt T . Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways: the ‘Dr. Jekyll and Mr. Hyde concept’ of Alzheimer's disease or the yin and yang of neuroplasticity. Prog Neurobiol.71, 83–284 (2003).
- Lee KH , LeeS-J , LeeHJet al. Amyloid β1-42 (Aβ1-42) induces the CDK2-mediated phosphorylation of Tau through the activation of the mTORC1 signaling pathway while promoting neuronal cell death. Front. Mol Neurosci.10, 229 (2017).
- Nygaard HB . Targeting Fyn kinase in Alzheimer's disease. Biol. Psychiatry83, 369–376 (2018).
- Qian D , LevS , van OersNS , DikicI , SchlessingerJ , WeissA. Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during the TCR signaling. J. Exp. Med.185, 1253–1259 (2015).
- Lee SK , LeeIH , KimHJ , ChangGS , ChungJE , NoKT. The PreADME Approach: web-based program for rapid prediction of physico-chemical, drug absorption and drug-like problems. EuroQSAR 2002 designing Drugs and Crop Protectants: processes, problems and solutions. Blackwell Publishing, MA, USA, 418–420 (2003).
- Norinder U , HaeberleinM. Computationsl approaches to the prediction of the blood-brain distribution. Advanced Drug Delivery Rev.54, 291–313 (2005).
- Ma X , ChenC , YangJ. Predictive model of blood-brain barrier penetration of organic compounds. Acta Pharmacol. Sin.26, 500–512 (2005).