Generic placeholder image

Central Nervous System Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

Review Article

Old Drugs with New Tricks: Paradigm in Drug Development Pipeline for Alzheimer’s Disease

Author(s): Tanay Dalvi, Bhaskar Dewangan, Rudradip Das, Jyoti Rani, Suchita D. Shinde, Nazmina Vhora, Alok Jain and Bichismita Sahu*

Volume 20, Issue 3, 2020

Page: [157 - 176] Pages: 20

DOI: 10.2174/1871524920666201021164805

Price: $65

Abstract

The most common reason behind dementia is Alzheimer’s disease (AD) and it is predicted to be the third life-threatening disease apart from stroke and cancer for the geriatric population. Till now, only four drugs are available on the market for symptomatic relief. The complex nature of disease pathophysiology and lack of concrete evidence of molecular targets are the major hurdles for developing a new drug to treat AD. The rate of attrition of many advanced drugs at clinical stages makes the de novo discovery process very expensive. Alternatively, Drug Repurposing (DR) is an attractive tool to develop drugs for AD in a less tedious and economic way. Therefore, continuous efforts are being made to develop a new drug for AD by repurposing old drugs through screening and data mining. For example, the survey in the drug pipeline for Phase III clinical trials (till February 2019) consists of 27 candidates, and around half of the number are drugs which have already been approved for other indications.

Although in the past, the drug repurposing process for AD has been reviewed in the context of disease areas, molecular targets, there is no systematic review of repurposed drugs for AD from the recent drug development pipeline (2019-2020). In this manuscript, we have reviewed the clinical candidates for AD with emphasis on their development history, including molecular targets and the relevance of the target for AD.

Keywords: Drug pipeline, drugs in clinical trials, Alzheimer's disease, drug repurposing, mechanism of action of drugs, cancer, diabetes, inflammation, neurodegeneration.

Graphical Abstract

[1]
Bakkour A, Morris JC, Wolk DA, Dickerson BC. The effects of aging and Alzheimer’s disease on cerebral cortical anatomy: Specificity and differential relationships with cognition. Neuroimage 2013; 76: 332-44.
[http://dx.doi.org/10.1016/j.neuroimage.2013.02.059] [PMID: 23507382]
[2]
Mu Y, Gage FH. Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener 2011; 6: 85.
[http://dx.doi.org/10.1186/1750-1326-6-85] [PMID: 22192775]
[3]
Cummings J, Feldman HH, Scheltens P. The “rights” of precision drug development for Alzheimer’s disease. Alzheimers Res Ther 2019; 11(1): 76.
[http://dx.doi.org/10.1186/s13195-019-0529-5] [PMID: 31470905]
[4]
Bethesda. Clinical and research information on drug induced liver injury. LiverTox. National Institute of Diabetes and Digestive and Kidney Diseases 2020; 2020: 1-8.
[5]
Hippius H, Neundörfer G. The discovery of Alzheimer’s disease. Dialogues Clin Neurosci 2003; 5(1): 101-8.
[PMID: 22034141]
[6]
Gaugler J, James B, Johnson T, Marin A, Weuve J. 2020 Alzheimer’s disease facts and figures. Alzheimers Dement 2020; 16: 391-460.
[http://dx.doi.org/10.1002/alz.12068] [PMID: 32157811]
[7]
Lundkvist J, Halldin MM, Sandin J, et al. The battle of Alzheimer’s disease- the beginning of the future unleashing the potential of academic discoveries. Front Pharmacol 2014; 5: 102.
[http://dx.doi.org/10.3389/fphar.2014.00102] [PMID: 24847271]
[8]
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: A systematic review and metaanalysis. Alzheimers Dement 2013; 9(1): 63-75.e2.
[http://dx.doi.org/10.1016/j.jalz.2012.11.007] [PMID: 23305823]
[9]
Sheena M. Posey Norris, Diana E. Pankevich, M. D.; Altevogt, B. M. International animal research regulations: Impact on Neuroscience Research: Workshop Summary 2012.
[10]
Osakwe O, Rizvi S. Trends in Innovation and the Business of Drug Discovery.In: Social Aspects of Drug Discovery, Development and Commercialization Academic Press: USA, 2016; pp. 29-55.
[http://dx.doi.org/10.1016/B978-0-12-802220-7.00002-8]
[11]
Hasin Y, Seldin M, Lusis A. Multi-omics approaches to disease. Genome Biol 2017; 18(1): 83.
[http://dx.doi.org/10.1186/s13059-017-1215-1] [PMID: 28476144]
[12]
Musa A, Ghoraie LS, Zhang SD, et al. A review of connectivity map and computational approaches in pharmacogenomics. Brief Bioinform 2018; 19(3): 506-23.
[PMID: 28069634]
[13]
Meng G, Meng X, Ma X, et al. Application of ferulic acid for Alzheimer’s disease: Combination of text mining and experimental validation. Front Neuroinform 2018; 12: 31.
[http://dx.doi.org/10.3389/fninf.2018.00031] [PMID: 29896095]
[14]
Chiesi AM. Network Analysis. Int Encycl Soc Behav Sci Second 2015; 16: 518-23.
[15]
Waring SC, Rosenberg RN. Genome-wide association studies in Alzheimer disease. Arch Neurol 2008; 65(3): 329-34.
[http://dx.doi.org/10.1001/archneur.65.3.329] [PMID: 18332245]
[16]
Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K. Alzheimer’s disease drug development pipeline: 2019. Alzheimer’s Dement Transl Res Clin Interv 2019; 5: 272-93.
[http://dx.doi.org/10.1016/j.trci.2019.05.008] [PMID: 31334330]
[17]
Rajasekhar K, Chakrabarti M, Govindaraju T. Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer’s disease. Chem Commun (Camb) 2015; 51(70): 13434-50.
[http://dx.doi.org/10.1039/C5CC05264E] [PMID: 26247608]
[18]
Hardy J. Alzheimer’s disease: The amyloid cascade hypothesis: An update and reappraisal. J Alzheimers Dis 2006; 9(3)(Suppl.): 151-3.
[http://dx.doi.org/10.3233/JAD-2006-9S317] [PMID: 16914853]
[19]
Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol 2018; 14: 450-64.
[http://dx.doi.org/10.1016/j.redox.2017.10.014] [PMID: 29080524]
[20]
Tamagno E, Guglielmotto M, Aragno M, et al. Oxidative stress activates a positive feedback between the γ- and β-secretase cleavages of the β-amyloid precursor protein. J Neurochem 2008; 104(3): 683-95.
[PMID: 18005001]
[21]
Shen C, Chen Y, Liu H, et al. Hydrogen peroxide promotes Abeta production through JNK-dependent activation of γ-secretase. J Biol Chem 2008; 283(25): 17721-30.
[http://dx.doi.org/10.1074/jbc.M800013200] [PMID: 18436531]
[22]
Tamagno E, Guglielmotto M, Monteleone D, Tabaton M. Amyloid-β production: Major link between oxidative stress and BACE1. Neurotox Res 2012; 22(3): 208-19.
[http://dx.doi.org/10.1007/s12640-011-9283-6] [PMID: 22002808]
[23]
Zhao Y, Zhao B. Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid Med Cell Longev 2013.2013316523
[http://dx.doi.org/10.1155/2013/316523] [PMID: 23983897]
[24]
Sambamurti K, Kinsey R, Maloney B, Ge Y-W, Lahiri DK. Gene structure and organization of the human beta-secretase (BACE) promoter. FASEB J 2004; 18(9): 1034-6.
[http://dx.doi.org/10.1096/fj.03-1378fje] [PMID: 15059975]
[25]
Yao M, Nguyen TVV, Pike CJ. β-amyloid-induced neuronal apoptosis involves c-Jun N-terminal kinase-dependent downregulation of Bcl-w. J Neurosci 2005; 25(5): 1149-58.
[http://dx.doi.org/10.1523/JNEUROSCI.4736-04.2005] [PMID: 15689551]
[26]
Gaggelli E, Kozlowski H, Valensin D, Valensin G. Copper homeostasis and neurodegenerative disorders (Alzheimer’s, prion, and Parkinson’s diseases and amyotrophic lateral sclerosis). Chem Rev 2006; 106(6): 1995-2044.
[http://dx.doi.org/10.1021/cr040410w] [PMID: 16771441]
[27]
Peterson LK, Fujinami RS. Inflammation, demyelination, neurodegeneration and neuroprotection in the pathogenesis of multiple sclerosis. J Neuroimmunol 2007; 184(1-2): 37-44.
[http://dx.doi.org/10.1016/j.jneuroim.2006.11.015] [PMID: 17196667]
[28]
Savelieff MG, Nam G, Kang J, Lee HJ, Lee M, Lim MH. Development of multifunctional molecules as potential therapeutic candidates for Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis in the last decade. Chem Rev 2019; 119(2): 1221-322.
[http://dx.doi.org/10.1021/acs.chemrev.8b00138] [PMID: 30095897]
[29]
Bennett DA, Yu L, De Jager PL. Building a pipeline to discover and validate novel therapeutic targets and lead compounds for Alzheimer’s disease. Biochem Pharmacol 2014; 88(4): 617-30.
[http://dx.doi.org/10.1016/j.bcp.2014.01.037] [PMID: 24508835]
[30]
Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: Progress, challenges and recommendations. Nat Rev Drug Discov 2019; 18(1): 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[31]
Naveja JJ, Dueñas-gonzález A, Medina-franco JL. Drug repurposing for epigenetic targets guided by computational methods. In:Epi-Informatics Academic Press: USA 2016; pp. 327-357.
[http://dx.doi.org/10.1016/B978-0-12-802808-7.00012-5]
[32]
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7(3): 263-9.
[http://dx.doi.org/10.1016/j.jalz.2011.03.005] [PMID: 21514250]
[33]
Gracon SI, Knapp MJ, Berghoff WG, et al. Safety of tacrine: clinical trials, treatment IND, and postmarketing experience. Alzheimer Dis Assoc Disord 1998; 12(2): 93-101.
[http://dx.doi.org/10.1097/00002093-199806000-00007] [PMID: 9651138]
[34]
Watkins PB, Zimmerman HJ, Knapp MJ, Gracon SI, Lewis KW. Hepatotoxic effects of tacrine administration in patients with Alzheimer’s disease. JAMA 1994; 271(13): 992-8.
[http://dx.doi.org/10.1001/jama.1994.03510370044030] [PMID: 8139084]
[35]
Shigeta M, Homma A. Donepezil for Alzheimer’s disease: Pharmacodynamic, pharmacokinetic, and clinical profiles. CNS Drug Rev 2001; 7(4): 353-68.
[http://dx.doi.org/10.1111/j.1527-3458.2001.tb00204.x] [PMID: 11830754]
[36]
Wilcock GK, Lilienfeld S, Gaens E. Efficacy and safety of galantamine in patients with mild to moderate Alzheimer’s disease: Multicentre randomised controlled trial. Galantamine International-1 Study Group. BMJ 2000; 321(7274): 1445-9.
[http://dx.doi.org/10.1136/bmj.321.7274.1445] [PMID: 11110737]
[37]
Grossberg GT, Desai AK. Management of Alzheimer’s disease. J Gerontol A Biol Sci Med Sci 2003; 58(4): 331-53.
[http://dx.doi.org/10.1093/gerona/58.4.M331] [PMID: 12663697]
[38]
Holzgrabe U, Kapková P, Alptüzün V, Scheiber J, Kugelmann E. Targeting Acetylcholinesterase to Treat Neurodegeneration. Expert Opin Ther Targets 2007; 11(2): 161-79.
[http://dx.doi.org/10.1517/14728222.11.2.161]
[39]
Scott TJ, O’Connor AC, Link AN, Beaulieu TJ. Economic analysis of opportunities to accelerate Alzheimer’s disease research and development. Ann N Y Acad Sci 2014; 1313: 17-34.
[http://dx.doi.org/10.1111/nyas.12417] [PMID: 24673372]
[40]
Cummings J, Reiber C, Kumar P. The price of progress: Funding and financing Alzheimer’s disease drug development. Alzheimer’s Dement Transl Res Clin Interv 2018; 4: 330-43.
[http://dx.doi.org/10.1016/j.trci.2018.04.008] [PMID: 30175227]
[41]
Christensen DD. Alzheimer’s disease: progress in the development of anti-amyloid disease-modifying therapies. CNS Spectr 2007; 12(2): 113-6.
[http://dx.doi.org/10.1017/S1092852900020629] [PMID: 17277711]
[42]
Langedijk J, Mantel-Teeuwisse AK, Slijkerman DS, Schutjens MH. Drug repositioning and repurposing: Terminology and definitions in literature. Drug Discov Today 2015; 20(8): 1027-34.
[http://dx.doi.org/10.1016/j.drudis.2015.05.001] [PMID: 25975957]
[43]
Antoszczak M, Markowska A, Markowska J, Huczyński A. Old wine in new bottles: Drug repurposing in oncology. Eur J Pharmacol 2020; 2020866172784
[http://dx.doi.org/10.1016/j.ejphar.2019.172784] [PMID: 31730760]
[44]
Li Y, Hu J, Wang Y, Zhou J, Zhang L, Liu Z. DeepScaffold: A Comprehensive tool for scaffold-based De novo drug discovery using deep learning. J Chem Inf Model 2020; 60(1): 77-91.
[http://dx.doi.org/10.1021/acs.jcim.9b00727] [PMID: 31809029]
[45]
Fischer T, Gazzola S, Riedl R, Fischer T, Gazzola S, Riedl R. Approaching target selectivity by De novo drug design. Expert Opin Drug Discov 2019; 14(8): 791-803.
[http://dx.doi.org/10.1080/17460441.2019.1615435] [PMID: 31179763]
[46]
Speck-planche A. Multi-scale modeling in drug discovery against infectious diseases. Mini Rev Med Chem 2019; 19(19): 1560-3.
[http://dx.doi.org/10.2174/138955751919191024110000]
[47]
Kato S, Moulder SL, Ueno NT, Wheler JJ. Meric-, F.; Kurzrock, R.; Janku, F. Challenges and perspective of drug repurposing strategies in early phase clinical trials. Oncoscience 2015; 2: 576-80.
[http://dx.doi.org/10.18632/oncoscience.173] [PMID: 26244164]
[48]
Ashburn TT, Thor KB. Drug repositioning: Identifying and developing new uses for existing drugs. Nat Rev Drug Discov 2004; 3(8): 673-83.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[49]
Almeida E, Oliveira M. De, Lang KL. Repositioning: Concept, classification, methodology, and importance in rare/orphans and neglected diseases. J Appl Pharm Sci 2018; 8: 157-65.
[50]
Tokunaga E, Yamamoto T, Ito E, Shibata N. Understanding the thalidomide chirality in biological processes by the self-disproportionation of enantiomers. Sci Rep 2018; 8(1): 17131.
[http://dx.doi.org/10.1038/s41598-018-35457-6] [PMID: 30459439]
[51]
Gupta SC, Sung B, Prasad S, Webb LJ, Aggarwal BB. Cancer drug discovery by repurposing: Teaching new tricks to old dogs. Trends Pharmacol Sci 2013; 34(9): 508-17.
[http://dx.doi.org/10.1016/j.tips.2013.06.005] [PMID: 23928289]
[52]
Zins GR. The history of the development of minoxidil. Clin Dermatol 1988; 6(4): 132-47.
[http://dx.doi.org/10.1016/0738-081X(88)90078-8] [PMID: 3063368]
[53]
Shoaib M, Kamal MA, Rizvi SMD. Repurposed drugs as potential therapeutic candidates for the management of Alzheimer’s disease. Curr Drug Metab 2017; 18(9): 842-52.
[http://dx.doi.org/10.2174/1389200218666170607101622] [PMID: 28595531]
[54]
Xue H, Li J, Xie H, Wang Y. review of drug repositioning approaches and resources. Int J Biol Sci 2018; 14(10): 1232-44.
[http://dx.doi.org/10.7150/ijbs.24612] [PMID: 30123072]
[55]
Madden A, Collins P, McGowan S, et al. Demonstrating the financial impact of clinical libraries: A systematic review. Health Info Libr J 2016; 33(3): 172-89.
[http://dx.doi.org/10.1111/hir.12151] [PMID: 27503690]
[56]
Hodos RA, Kidd BA, Khader S, Redhead BP, Dudley JT. Computational approaches to drug repurposing and pharmacology. Wiley Interdiscip Rev Syst Biol Med 2016; 8: 186-210.
[http://dx.doi.org/10.1002/wsbm.1337] [PMID: 27080087]
[57]
Yella JK, Yaddanapudi S, Wang Y, Jegga AG. changing trends in computational drug repositioning. Pharmaceuticals 2018; 11(2): 57-78.
[http://dx.doi.org/10.3390/ph11020057] [PMID: 29874824]
[58]
Savva K, Zachariou M, Oulas A, et al. Computational drug repurposing for neurodegenerative diseases.In: silico drug design Academic Press: USA, 2019; pp. 85-118.
[http://dx.doi.org/10.1016/B978-0-12-816125-8.00004-3]
[59]
(a)Paranjpe MD, Taubes A, Sirota M. Insights Into Computational Drug Repurposing For Neurodegenerative Disease Trends Pharmacol Sci 2019; 40(8): 565-76.
[http://dx.doi.org/10.1016/j.tips.2019.06.003] [PMID: 31326236] ; (b)John C. Siavelis, Marilena M. Bourdakou, Emmanouil I. Athanasiadis, George M. Spyrou and Konstantina S. Nikita. Brief Bioinform 17(2), 2016, 322–335
[http://dx.doi.org/10.1093/bib/bbv048]
[60]
Alvarez JC. High-throughput docking as a source of novel drug leads. Curr Opin Chem Biol 2004; 8(4): 365-70.
[http://dx.doi.org/10.1016/j.cbpa.2004.05.001] [PMID: 15288245]
[61]
Kumar S, Chowdhury S, Kumar S. In silico repurposing of antipsychotic drugs for Alzheimer’s disease. BMC Neurosci 2017; 18(1): 76.
[http://dx.doi.org/10.1186/s12868-017-0394-8] [PMID: 29078760]
[62]
Bakkar N, Kovalik T, Lorenzini I, et al. Artificial intelligence in neurodegenerative disease research: Use of IBM Watson to identify additional RNA-binding proteins altered in amyotrophic lateral sclerosis. Acta Neuropathol 2018; 135(2): 227-47.
[http://dx.doi.org/10.1007/s00401-017-1785-8] [PMID: 29134320]
[63]
Napolitano F, Zhao Y, Moreira VM, et al. Drug repositioning: A machine-learning approach through data integration. J Cheminform 2013; 5(1): 30.
[http://dx.doi.org/10.1186/1758-2946-5-30] [PMID: 23800010]
[64]
Hema Sree GNS, Ganesan Rajalekshmi S, Murahari M, Burri RR. Reappraisal of FDA approved drugs against alzheimer’s disease based on differential gene expression and protein interaction network analysis: An in silico approach. J Biomol Struct Dyn 2019; 2019: 1-18.
[PMID: 31543038]
[65]
Hassan M, Abbasi MA, Siddiqui AS, et al. Designing of promising medicinal scaffolds for Alzheimer’s disease through enzyme inhibition, lead optimization, molecular docking and dynamic simulation approaches. Bioorg Chem 2019; 91: 1-11.
[http://dx.doi.org/10.1016/j.bioorg.2019.103138]
[66]
Staropoli JF. Tumorigenesis and neurodegeneration: Two sides of the same coin? BioEssays 2008; 30(8): 719-27.
[http://dx.doi.org/10.1002/bies.20784] [PMID: 18623069]
[67]
Holohan KN, Lahiri DK, Schneider BP, Foroud T, Saykin AJ. Functional microRNAs in Alzheimer’s disease and cancer: Differential regulation of common mechanisms and pathways. Front Genet 2013; 3: 323.
[http://dx.doi.org/10.3389/fgene.2012.00323] [PMID: 23335942]
[68]
Fischer R, Maier O. Interrelation of oxidative stress and inflammation in neurodegenerative disease: Role of TNF. Oxid Med Cell Longev 2015; 2015610813
[http://dx.doi.org/10.1155/2015/610813] [PMID: 25834699]
[69]
Majd S, Power J, Majd Z. Alzheimer’s disease and Cancer: When two monsters cannot be together. Front Neurosci 2019; 13: 155.
[http://dx.doi.org/10.3389/fnins.2019.00155] [PMID: 30881282]
[70]
Mastroeni D, Grover A, Delvaux E, Whiteside C, Coleman PD, Rogers J. Epigenetic mechanisms in Alzheimer’s disease. Neurobiol Aging 2011; 32(7): 1161-80.
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.08.017] [PMID: 21482442]
[71]
Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH. Recovery of learning and memory is associated with chromatin remodelling. Nature 2007; 447(7141): 178-82.
[http://dx.doi.org/10.1038/nature05772] [PMID: 17468743]
[72]
Wei Y, Shin MR, Sesti F. Oxidation of KCNB1 channels in the human brain and in mouse model of Alzheimer’s disease. Cell Death Dis 2018; 9(8): 820.
[http://dx.doi.org/10.1038/s41419-018-0886-1] [PMID: 30050035]
[73]
Ryu KY, Lee HJ, Woo H, et al. Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT/STAT3 signaling. J Neuroinflammation 2019; 16(1): 190.
[http://dx.doi.org/10.1186/s12974-019-1561-x] [PMID: 31655606]
[74]
Zhang P, Kishimoto Y, Grammatikakis I, et al. Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer’s disease model. Nat Neurosci 2019; 22(5): 719-28.
[http://dx.doi.org/10.1038/s41593-019-0372-9] [PMID: 30936558]
[75]
Musi N. Senolytic Therapy to Modulate Progression of Alzheimer’s Disease (SToMP-AD). San Antonio, Texas, United States 2020.
[76]
Turner RS, Hebron ML, Lawler A, et al. Nilotinib effects on safety, tolerability, and biomarkers in Alzheimer’s disease. Ann Neurol 2020; 88(1): 183-94.
[http://dx.doi.org/10.1002/ana.25775] [PMID: 32468646]
[77]
Marks PA, Breslow R. Dimethyl sulfoxide to vorinostat: Development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 2007; 25(1): 84-90.
[http://dx.doi.org/10.1038/nbt1272] [PMID: 17211407]
[78]
Richon VM. Cancer biology: Mechanism of antitumour action of Vorinostat (Suberoylanilide Hydroxamic Acid), a novel histone deacetylase inhibitor. Br J Cancer 2006; 95: 2-6.
[http://dx.doi.org/10.1038/sj.bjc.6603463]
[79]
Xu K, Dai XL, Huang HC, Jiang ZF. Targeting HDACs: A promising therapy for Alzheimer’s disease. Oxid Med Cell Longev 2011; 2011143269
[http://dx.doi.org/10.1155/2011/143269] [PMID: 21941604]
[80]
US National Liberary of Medicine. Clinical trial to determine tolerable doses of Vorinostat in patients with mild Alzheimer disease (VostatAD01) 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT03056495
[81]
Caraci F, Leggio GM, Drago F, Salomone S. Epigenetic drugs for Alzheimer’s disease: Hopes and challenges. Br J Clin Pharmacol 2013; 75(4): 1154-5.
[http://dx.doi.org/10.1111/j.1365-2125.2012.04443.x] [PMID: 22905960]
[82]
Cole G, Dobkins KR, Hansen LA, Terry RD, Saitoh T. Decreased levels of protein kinase C in Alzheimer brain. Brain Res 1988; 452(1-2): 165-74.
[http://dx.doi.org/10.1016/0006-8993(88)90021-2] [PMID: 3165303]
[83]
Crasto AM. Masitinib. Available from: https://newdrugapprovals.org/2015/05/22/masitinib-2/
[84]
Folch J, Petrov D, Ettcheto M, et al. Masitinib for the treatment of mild to moderate Alzheimer’s disease. Expert Rev Neurother 2015; 15(6): 587-96.
[http://dx.doi.org/10.1586/14737175.2015.1045419] [PMID: 25961655]
[85]
Jash K, Gondaliya P, Kirave P, Kulkarni B, Sunkaria A, Kalia K. Cognitive dysfunction: A growing link between diabetes and Alzheimer’s disease. Drug Dev Res 2019; 2019: 1-21.
[http://dx.doi.org/10.1002/ddr.21579] [PMID: 31820484]
[86]
Baglietto-Vargas D, Shi J, Yaeger DM, Ager R, LaFerla FM. Diabetes and Alzheimer’s disease crosstalk. Neurosci Biobehav Rev 2016; 64: 272-87.
[http://dx.doi.org/10.1016/j.neubiorev.2016.03.005] [PMID: 26969101]
[87]
Lee HJ, Seo HI, Cha HY, Yang YJ, Kwon SH, Yang SJ. Diabetes and Alzheimer’s disease: Mechanisms and nutritional aspects. Clin Nutr Res 2018; 7(4): 229-40.
[http://dx.doi.org/10.7762/cnr.2018.7.4.229] [PMID: 30406052]
[88]
Yang Y, Wu Y, Zhang S, Song W. High glucose promotes Aβ production by inhibiting APP degradation. PLoS One 2013; 8(7)e69824
[http://dx.doi.org/10.1371/journal.pone.0069824] [PMID: 23894546]
[89]
Mudaliar SR, Lindberg FA, Joyce M, et al. Insulin aspart (B28 asp-insulin): A fast-acting analog of human insulin: Absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects. Diabetes Care 1999; 22(9): 1501-6.
[http://dx.doi.org/10.2337/diacare.22.9.1501] [PMID: 10480516]
[90]
Morris JK, Burns JM. Insulin: an emerging treatment for Alzheimer’s disease dementia? Curr Neurol Neurosci Rep 2012; 12(5): 520-7.
[http://dx.doi.org/10.1007/s11910-012-0297-0] [PMID: 22791280]
[91]
Freiherr J, Hallschmid M, Frey WH II, et al. Intranasal insulin as a treatment for Alzheimer’s disease: A review of basic research and clinical evidence. CNS Drugs 2013; 27(7): 505-14.
[http://dx.doi.org/10.1007/s40263-013-0076-8] [PMID: 23719722]
[92]
Craft S. Study of nasal insulin to fight forgetfulness - device comparison study. North Carolina 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT03857321
[93]
Gurgle HE, White K, McAdam-Marx C. SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy in type 2 diabetes: Patient selection and perspectives. Vasc Health Risk Manag 2016; 12: 239-49.
[PMID: 27350752]
[94]
Rizvi SMD, Shaikh S, Waseem SMA, et al. Role of anti-diabetic drugs as therapeutic agents in Alzheimer’s disease. EXCLI J 2015; 14: 684-96.
[PMID: 27152105]
[95]
Edison P. Evaluating liraglutide in Alzheimer’s disease London: ELAD 2013. Available from: https://clinicaltrials.gov/ct2/show/NCT01843075
[96]
Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, de Leon MJ. Inflammation and Alzheimer’s disease: Possible role of periodontal diseases. Alzheimers Dement 2008; 4(4): 242-50.
[http://dx.doi.org/10.1016/j.jalz.2007.08.004] [PMID: 18631974]
[97]
Landreth G, Combs C, Karlo JC, Sundararajan S. Inflammatory mechanisms in Alzheimer’s disease: β-amyloid-stimulated proinflammatory responses are blocked by PPARγ agonists. J Neurosci 2002; 20: 163-8.
[98]
Chiroma SM, Baharuldin MTH, Taib CNM, Amom Z, Jagadeesan S, Moklas MAM. Inflammation in Alzheimer’s disease: A friend or foe? Biomed Res Ther 2018; 5: 2552-64.
[http://dx.doi.org/10.15419/bmrat.v5i8.464]
[99]
Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol 2015; 14(4): 388-405.
[http://dx.doi.org/10.1016/S1474-4422(15)70016-5] [PMID: 25792098]
[100]
Anderson K, Wherle L, Park M, Nelson K, Nguyen L. Salsalate, an old, inexpensive drug with potential new indications: A review of the evidence from 3 recent studies. Am Health Drug Benefits 2014; 7(4): 231-5.
[PMID: 25126374]
[101]
Crofford LJ. Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther 2013; 15(Suppl. 3): S2.
[http://dx.doi.org/10.1186/ar4174] [PMID: 24267197]
[102]
Medina M. An overview on the clinical development of tau-based therapeutics. Int J Mol Sci 2018; 19(4): 1-14.
[http://dx.doi.org/10.3390/ijms19041160] [PMID: 29641484]
[103]
Min S-W, Cho S-H, Zhou Y, et al. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 2010; 67(6): 953-66.
[http://dx.doi.org/10.1016/j.neuron.2010.08.044] [PMID: 20869593]
[104]
Virchow JC, Bachert C. Efficacy and safety of montelukast in adults with asthma and allergic rhinitis. Respir Med 2006; 100(11): 1952-9.
[http://dx.doi.org/10.1016/j.rmed.2006.02.026] [PMID: 16626955]
[105]
Hon KLE, Leung TF, Leung AKC. What Are the conclusions from clinical trials and meta-analyses. Clinical effectiveness and safety of montelukast in asthma. What are the conclusions from clinical trials and meta-analyses? Drug Des Devel Ther 2014; 8: 839-50.
[http://dx.doi.org/10.2147/DDDT.S39100] [PMID: 25061277]
[106]
Lai J, Mei ZL, Wang H, et al. Montelukast rescues primary neurons against Aβ1-42-induced toxicity through inhibiting CysLT1R-mediated NF-κB signaling. Neurochem Int 2014; 75: 26-31.
[http://dx.doi.org/10.1016/j.neuint.2014.05.006] [PMID: 24879954]
[107]
Tang SS, Wang XY, Hong H, et al. Leukotriene D4 induces cognitive impairment through enhancement of CysLT1 R-mediated amyloid-β generation in mice. Neuropharmacology 2013; 65: 182-92.
[http://dx.doi.org/10.1016/j.neuropharm.2012.08.026] [PMID: 22982445]
[108]
Wang XY, Tang SS, Hu M, et al. Leukotriene D4 induces amyloid-β generation via CysLT(1)R-mediated NF-κB pathways in primary neurons. Neurochem Int 2013; 62(3): 340-7.
[http://dx.doi.org/10.1016/j.neuint.2013.01.002] [PMID: 23318673]
[109]
Lai J, Hu M, Wang H, et al. Montelukast targeting the cysteinyl leukotriene receptor 1 ameliorates Aβ1-42-induced memory impairment and neuroinflammatory and apoptotic responses in mice. Neuropharmacology 2014; 79: 707-14.
[http://dx.doi.org/10.1016/j.neuropharm.2014.01.011] [PMID: 24456746]
[110]
Licastro F, Carbone I, Raschi E, Porcellini E. The 21st century epidemic: Infections as inductors of neuro-degeneration associated with Alzheimer’s Disease. Immun Ageing 2014; 11(1): 22.
[http://dx.doi.org/10.1186/s12979-014-0022-8] [PMID: 25516763]
[111]
Deatly AM, Haase AT, Fewster PH, Lewis E, Ball MJ. Human herpes virus infections and Alzheimer’s disease. Neuropathol Appl Neurobiol 1990; 16(3): 213-23.
[http://dx.doi.org/10.1111/j.1365-2990.1990.tb01158.x] [PMID: 2169597]
[112]
Balin BJ, Hudson AP. Herpes viruses and Alzheimer’s disease: New evidence in the debate. Lancet Neurol 2018; 17(10): 839-41.
[http://dx.doi.org/10.1016/S1474-4422(18)30316-8] [PMID: 30264721]
[113]
Rakhmanina NY, van den Anker JN. Efavirenz in the therapy of HIV infection. Expert Opin Drug Metab Toxicol 2010; 6(1): 95-103.
[http://dx.doi.org/10.1517/17425250903483207] [PMID: 20001610]
[114]
Bittner C, Busemann AS, Griesbach U, et al. Efavirenz (Merck, DuPont 1999). Org Synth Workb 2001; II: 71-84.
[http://dx.doi.org/10.1002/3527600132.ch5]
[115]
Duwal S, Seeler D, Dickinson L, Khoo S, von Kleist M. The utility of Efavirenz-based prophylaxis against HIV infection. A systems pharmacological analysis. Front Pharmacol 2019; 10: 199.
[http://dx.doi.org/10.3389/fphar.2019.00199] [PMID: 30918485]
[116]
Mast N, Saadane A, Valencia-Olvera A, et al. Cholesterol-metabolizing enzyme cytochrome P450 46A1 as a pharmacologic target for Alzheimer’s disease. Neuropharmacology 2017; 123: 465-76.
[http://dx.doi.org/10.1016/j.neuropharm.2017.06.026] [PMID: 28655608]
[117]
Anderson KW, Mast N, Hudgens JW, Lin JB, Turko IV, Pikuleva IA. Mapping of the allosteric site in cholesterol hydroxylase CYP46A1 for Efavirenz, a drug that stimulates enzyme activity. J Biol Chem 2016; 291(22): 11876-86.
[http://dx.doi.org/10.1074/jbc.M116.723577] [PMID: 27056331]
[118]
Pikuleva IA. Efav irenz for patients with Alzheimer’s disease Available from: https://clinicaltrials.gov/ct2/show/NCT03706885

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy