Receptor-based approaches and therapeutic targets in Alzheimer’s disease along with role of AI in drug designing: Unraveling pathologies and advancing treatment strategies

Mohsina Patwekar, Faheem Patwekar, Daniyal Shaikh, Shaikh Rohin Fatema, Sunil J. Aher, Rohit Sharma

Article ID: 2338
Vol 6, Issue 3, 2023

VIEWS - 419 (Abstract) 95 (PDF)


Alzheimer’s disease (AD) is a prevalent cause of dementia in the elderly, characterized by progressive cognitive decline and neurodegeneration. This review focuses on the etiology of AD, the role of various receptors [TNF (Tumor necrosis factor) receptor, nAChR (Neuronal nicotinic acetylcholine receptors), NMDARs (N-Methyl-D-aspartate receptors), APOE (Apolipoprotein E) receptor, and amyloid-beta receptor], and risk factors contributing to its development. AD progresses through mild, moderate, and severe stages, each exhibiting distinct symptoms. The hallmark pathologies are neurofibrillary tangles and amyloid plaques, comprised of hyperphosphorylated tau protein and amyloid-beta peptides, respectively. Current pharmacotherapeutic options alleviate symptoms but lack a complete cure. To address the challenges in developing effective AD treatments, researchers have turned to artificial intelligence (AI) and computational approaches in drug design. AI techniques, including machine learning and molecular docking, enable the analysis of large datasets and prediction of molecular interactions between potential drug candidates and target receptors. Virtual screening and molecular modeling aid in identifying novel therapeutic compounds. Predictive modeling and optimization algorithms optimize drug properties and predict efficacy. AI also facilitates the repurposing of existing drugs by analyzing their interactions with AD-related receptors and pathways. Clinical trial optimization using AI algorithms enhances patient selection, treatment monitoring, and outcome prediction. Integrating AI into AD drug design holds tremendous promise for accelerating the discovery of effective interventions. By leveraging AI’s capabilities, researchers can efficiently analyze extensive data, predict drug-target interactions, and optimize drug properties, leading to the identification of novel AD treatments. However, further research and validation are needed to translate AI-driven drug design approaches into clinically viable solutions for AD patients. Through continued advancements in AI and collaborative efforts, the development of targeted and advanced therapies for AD is within reach.


Alzheimer’s disease; receptors; computational approach; artificial intelligence

Full Text:



1. Hane FT, Robinson M, Lee BY, et al. Recent progress in Alzheimer’s disease research, part 3: Diagnosis and treatment. Journal of Alzheimer’s Disease 2017; 57(3): 645–665. doi: 10.3233/JAD-160907

2. Khan MM, Ahsan F, Ahmad U, et al. Alzheimer disease: A review. World Journal of Pharmacy and Pharmaceutical Sciences 2016; 5(6): 649–666. doi: 10.20959/wjpps20166-7045

3. Bhushan I, Kour M, Kour G, et al. Alzheimer’s disease: Causes & treatment—A review. Annals of Biotechnology 2018; 1(1): 1002. doi: 10.33582/2637-4927/1002

4. Wortmann M. Dementia: A global health priority-highlights from an ADI and World Health Organization report. Alzheimer’s Research & Therapy 2012; 4: 40. doi: 10.1186/alzrt143

5. Povova J, Ambroz P, Bar M, et al. Epidemiological of and risk factors for Alzheimer’s disease: A review. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czech Republic 2012; 156(2): 108–114. doi: 10.5507/bp.2012.055

6. Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. The Lancet 2006; 368(9533): 387–403. doi: 10.1016/S0140-6736(06)69113-7

7. Kalaria RN, Maestre GE, Arizaga R, et al. Alzheimer’s disease and vascular dementia in developing countries: Prevalence, management, and risk factors. The Lancet Neurology 2008; 7(9): 812–826. doi: 10.1016/S1474-4422(08)70169-8

8. Platzer K, Yuan H, Schütz H, et al. GRIN2B encephalopathy: Novel findings on phenotype, variant clustering, functional consequences and treatment aspects. Journal of Medical Genetics 2017; 54(7): 460–470. doi: 10.1136/jmedgenet-2016-104509

9. Cummings JL, Vinters HV, Cole GM, Khachaturian ZS. Alzheimer’s disease: Etiologies, pathophysiology, cognitive reserve, and treatment opportunities. Neurology 1998; 51(1 Suppl 1): S65–S67. doi: 10.1212/wnl.51.1_suppl_1.s2

10. Seripa D, Matera MG, Franceschi M, et al. The RELN locus in Alzheimer’s disease. Journal of Alzheimer’s Disease 2008; 14(3): 335–344. doi: 10.3233/jad-2008-14308

11. Blacker D, Albert MS, Bassett SS, et al. Reliability and validity of NINCDS-ADRDA criteria for Alzheimer’s disease: The National Institute of Mental Health Genetics Initiative. Archives of Neurology 1994; 51(12): 1198–204. doi: 10.1001/archneur.1994.00540240042014

12. Lopez OL, Swihart AA, Becker JT, et al. Reliability of NINCDS‐ADRDA clinical criteria for the diagnosis of Alzheimer’s disease. Neurology 1990; 40(10): 1517–1522. doi: 10.1212/wnl.40.10.1517

13. DeMaagd G, Philip A. Parkinson’s Disease and Its Management: Part 1: Disease Entity, Risk Factors, Pathophysiology, Clinical Presentation, and Diagnosis. P T. 2015 Aug;40(8):504-32. PMID: 26236139; PMCID: PMC4517533.

14. Alzheimer’s Association. 2019 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia 2019; 15(3): 321–387. doi: 10.1016/j.jalz.2019.01.010

15. Gantela P, Ilankumaran S, Arunachalam M, et al. Analysis of Alzheimer disease with K means algorithm and PSO segmentation. In: Proceedings of the 2022 IEEE 2nd Mysore Sub Section International Conference (MysuruCon); 16 October 2022; Mysuru, India. pp. 1–6.

16. Savova GK, Masanz JJ, Ogren PV, et al. Mayo clinical text analysis and knowledge extraction system (cTAKES): Architecture, component evaluation and applications. Journal of the American Medical Informatics Association 2010; 17(5): 507–513. doi: 10.1136/jamia.2009.001560

17. Zhao L. CD33 in Alzheimer’s disease—Biology, pathogenesis, and therapeutics: A mini-review. Gerontology 2019; 65(4): 323–331. doi: 10.1159/000492596

18. Ding J, Eigenbrodt ML, Mosley Jr TH, et al. Alcohol intake and cerebral abnormalities on magnetic resonance imaging in a community-based population of middle-aged adults: The Atherosclerosis Risk in Communities (ARIC) study. Stroke 2004; 35(1): 16–21. doi: 10.1161/01.STR.0000105929.88691.8E

19. Paul CA, Au R, Fredman L, Massaro JM, et al. Association of alcohol consumption with brain volume in the Framingham study. Archives of Neurology 2008; 65(10): 1363–1367. doi: 10.1001/archneur.65.10.1363

20. Anttila T, Helkala EL, Viitanen M, et al. Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: A prospective population based study. BMJ 2004; 329(7465): 539. doi: 10.1136/bmj.38181.418958.BE

21. Ott A, Slooter AJ, Hofman A, et al. Smoking and risk of dementia and Alzheimer’s disease in a population-based cohort study: The Rotterdam study. The Lancet 1998; 351(9119): 1840–1843. doi: 10.1016/s0140-6736(97)07541-7

22. Merchant C, Tang MX, Albert S, et al. The influence of smoking on the risk of Alzheimer’s disease. Neurology 1999; 52(7): 1408–1412. doi: 10.1212/wnl.52.7.1408

23. Aggarwal NT, Bienias JL, Bennett DA, et al. The relation of cigarette smoking to incident Alzheimer’s disease in a biracial urban community population. Neuroepidemiology 2006; 26(3): 140–146. doi: 10.1159/000091654

24. Almeida OP, Hulse GK, Lawrence D, Flicker L. Smoking as a risk factor for Alzheimer’s disease: Contrasting evidence from a systematic review of case-control and cohort studies. Addiction 2002; 97(1): 15–28. doi: 10.1046/j.1360-0443.2002.00016.x

25. Ridge PG, Ebbert MTW, Kauwe JSK. Genetics of Alzheimer’s disease. BioMed Research International 2013; 2013: 254954. doi: 10.1155/2013/254954

26. Myers A, Holmans P, Marshall H, Kwon J, Meyer D, Ramic D, Shears S, Booth J, DeVrieze FW, Crook R, Hamshere M. Susceptibility locus for Alzheimer’s disease on chromosome 10. Science. 2000 Dec 22;290(5500):2304-5.

27. Noviandy TR, Maulana A, Idroes GM, et al. Integrating genetic algorithm and LightGBM for QSAR modeling of acetylcholinesterase inhibitors in Alzheimer’s disease drug discovery. Malacca Pharmaceutics 2023; 1(2): 48–54. doi: 10.60084/mp.v1i2.60

28. Barnard ND, Bunner AE, Agarwal U. Saturated and trans fats and dementia: A systematic review. Neurobiology of Aging 2014; 35: S65–S73. doi: 10.1016/j.neurobiolaging.2014.02.030

29. Morris MC, Tangney CC. Dietary fat composition and dementia risk. Neurobiology of Aging 2014; 35(Suppl 2): S59–S64. doi: 10.1016/j.neurobiolaging.2014.03.038

30. Maesako M, Uemura M, Tashiro Y, et al. High fat diet enhances β-site cleavage of amyloid precursor protein (APP) via promoting β-site APP cleaving enzyme 1/adaptor protein 2/clathrin complex formation. PLoS One 2015; 10(9): e0131199. doi: 10.1371/journal.pone.0131199

31. Knight EM, Martins IVA, Gümüsgöz S, et al. High-fat diet-induced memory impairment in triple-transgenic Alzheimer’s disease (3xTgAD) mice is independent of changes in amyloid and tau pathology. Neurobiology of Aging 2014; 35(8): 1821–1832. doi: 10.1016/j.neurobiolaging.2014.02.010

32. Patwekar M, Patwekar F, Mezni A, et al. Assessment of antioxidative and alpha-amylase potential of polyherbal extract. Evidence-Based Complementary and Alternative Medicine 2022; 2022: 7153526. doi: 10.1155/2022/7153526

33. Dias IHK, Polidori MC, Griffiths HR. Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier. Biochemical Society Transactions 2014; 42(4): 1001–1005. doi: 10.1042/BST20140164

34. Lim WLF, Martins IJ, Martins RN. The involvement of lipids in Alzheimer’s disease. Journal of Genetics and Genomics 2014; 41(5): 261–274. doi: 10.1016/j.jgg.2014.04.003

35. Mittelman MS, Roth DL, Coon DW, Haley WE. Sustained benefit of supportive intervention for depressive symptoms in caregivers of patients with Alzheimer’s disease. American Journal of Psychiatry 2004; 161(5): 850–856. doi: 10.1176/appi.ajp.161.5.850

36. Kosari S, Badoer E, Nguyen JCD, et al. Effect of western and high fat diets on memory and cholinergic measures in the rat. Behavioural Brain Research 2012; 235(1): 98–103. doi: 10.1016/j.bbr.2012.07.017

37. Butterfield DA, Di Domenico F, Barone E. Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2014; 1842(9): 1693–1706. doi: 10.1016/j.bbadis.2014.06.010

38. Mittal K, Katare DP. Shared links between type 2 diabetes mellitus and Alzheimer’s disease: A review. Diabetes & Metabolic Syndrome 2016; 10(2 Suppl 1): S144–S149. doi: 10.1016/j.dsx.2016.01.021

39. Rosales-Corral S, Tan DX, Manchester L, Reiter RJ. Diabetes and Alzheimer disease, two overlapping pathologies with the same background: Oxidative stress. Oxidative Medicine and Cellular Longevity 2015; 2015: 985845. doi: 10.1155/2015/985845

40. Joas E, Bäckman K, Gustafson D, et al. Blood pressure trajectories from midlife to late life in relation to dementia in women followed for 37 years. Hypertension 2012; 59(4): 796–801. doi: 10.1161/HYPERTENSIONAHA.111.182204

41. Birnbaum JH, Bali J, Rajendran L, et al. Calcium flux-independent NMDA receptor activity is required for Aβ oligomer-induced synaptic loss. Cell Death & Disease 2015; 6(6): e1791. doi: 10.1038/cddis.2015.160

42. Dos Santos Picanco LC, Ozela PF, de Fatima de Brito Brito M, et al. Alzheimer’s disease: A review from the pathophysiology to diagnosis, new perspectives for pharmacological treatment. Current Medicinal Chemistry 2018; 25(26): 3141–3159. doi: 10.2174/0929867323666161213101126

43. World Health Organization. mhGAP: Mental Health Gap Action Programme: scaling up care for mental, neurological and substance use disorders. World Health Organization; 2008.

44. Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer’s disease. The Lancet 1976; 2(8000): 1403. doi: 10.1016/s0140-6736(76)91936-x

45. McGeer PL, McGeer EG, Suzuki J, et al. Aging, Alzheimer’s disease, and the cholinergic system of the basal forebrain. Neurology 1984; 34(6): 741–745. doi: 10.1212/wnl.34.6.741

46. Muir JL. Acetylcholine, aging, and Alzheimer’s disease. Pharmacology Biochemistry and Behavior 1997; 56(4): 687–696. doi: 10.1016/s0091-3057(96)00431-5

47. Gotti C, Clementi F. Neuronal nicotinic receptors: From structure to pathology. Progress in Neurobiology 2004; 74(6): 363–396. doi: 10.1016/j.pneurobio.2004.09.006

48. Karlin A. Emerging structure of the nicotinic acetylcholine receptors. Nature Reviews Neuroscience 2002; 3(2): 102–114. doi: 10.1038/nrn731

49. Wevers A, Schröder H. Nicotinic acetylcholine receptors in Alzheimer’s disease. Journal of Alzheimer’s Disease 1999; 1(4–5): 207–219. doi: 10.3233/jad-1999-14-503

50. Quazi A, Mohsina FP, Faheem IP, Priya S. Silico ADMET analysis, molecular docking and in vivo anti diabetic activity of polyherbal tea bag formulation in streptozotocin-nicotinamide induced diabetic rats. International Journal of Health Sciences 2022; 6(S3): 343–372. doi: 10.53730/ijhs.v6nS3.5189

51. Mayer ML, Westbrook GL, Guthrie PB. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 1984; 309(5965): 261–263. doi: 10.1038/309261a0

52. Liu J, Chang L, Song Y, et al. The role of NMDA receptors in Alzheimer’s disease. Frontiers in Neuroscience 2019; 13: 43. doi: 10.3389/fnins.2019.00043

53. Wang R, Reddy PH. Role of glutamate and NMDA receptors in Alzheimer’s disease. Journal of Alzheimer’s Disease 2017; 57(4): 1041–1048. doi: 10.3233/JAD-160763

54. Fuchs P, Strehl S, Dworzak M, et al. Structure of the human TNF receptor 1 (p60) gene (TNRF1) and localization to chromosome 12p13. Genomics 1992; 13(1): 219–224. doi: 10.1016/0888-7543(92)90226-I

55. Loetscher H, Pan YC, Lahm HW, et al. Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor. Cell 1990; 61(2): 351–359. doi: 10.1016/0092-8674(90)90815-v

56. Santee SM, Owen-Schaub LB. Human tumor necrosis factor receptor p75/80 (CD120b) gene structure and promoter characterization. Journal of Biological Chemistry 1996; 271(35): 21151–21159. doi: 10.1074/jbc.271.35.21151

57. Schall TJ, Lewis M, Koller KJ, et al. Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell 1990; 61(2): 361–370. doi: 10.1016/0092-8674(90)90816-w

58. Smith CA, Davis T, Anderson D, et al. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 1990; 248(4958): 1019–1023. doi: 10.1126/science.2160731

59. Perry RT, Collins JS, Wiener H, et al. The role of TNF and its receptors in Alzheimer’s disease. Neurobiology of Aging 2001; 22(6): 873–883. doi: 10.1016/s0197-4580(01)00291-3

60. Bongioanni P, Romano MR, Sposito R, et al. T-cell tumour necrosis factor-alpha receptor binding in demented patients. Journal of Neurology 1997; 244(7): 418–425. doi: 10.1007/s004150050115

61. Sipe JD, Cohen AS. Review: History of the amyloid fibril. Journal of Structural Biology 2000; 130(2–3): 88–98. doi: 10.1006/jsbi.2000.4221

62. Glenner GG, Wong CW. Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochemical and Biophysical Research Communications 1984; 120(3): 885–890. doi: 10.1016/s0006-291x(84)80190-4

63. Jagust W. Imaging the evolution and pathophysiology of Alzheimer disease. Nature Reviews Neuroscience 2018; 19(11): 687–700. doi: 10.1038/s41583-018-0067-3

64. Lacor PN, Buniel MC, Furlow PW, et al. Aβ oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer’s disease. Journal of Neuroscience 2007; 27(4): 796–807. doi: 10.1523/JNEUROSCI.350106.2007

65. Shankar GM, Bloodgood BL, Townsend M, et al. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. Journal of Neuroscience 2007; 27(11): 2866–2875. doi: 10.1523/ JNEUROSCI.4970-06.2007

66. Wu HY, Hudry E, Hashimoto T, et al. Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation. Journal of Neuroscience 2010; 30(7): 2636–2349. doi: 10.1523/JNEUROSCI.4456-09.2010

67. Palop JJ, Mucke L. Amyloid-beta-induced neuronal dysfunction in Alzheimer’s disease: From synapses toward neural networks. Nature Neuroscience 2010; 13(7): 812–818. doi: 10.1038/nn.2583

68. Mahley RW. Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology. Science 1988; 240(4852): 622–630. doi: 10.1126/science.3283935

69. Strittmatter WJ, Saunders AM, Schmechel D, et al. Apolipoprotein E: High-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proceedings of the National Academy of Sciences 1993; 90(5): 1977–1981. doi: 10.1073/pnas.90.5.1977

70. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small G, Roses AD, Haines JL, Pericak-Vance MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993 Aug 13;261(5123):921-3.

71. Herz J, Bock HH. Lipoprotein receptors in the nervous system. Annual review of biochemistry 2002; 71(1): 405–434. doi: 10.1146/annurev.biochem.71.110601.135342

72. Pitas RE, Boyles JK, Lee SH, et al. Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism 1987; 917(1): 148–161. doi: 10.1016/0005-2760(87)90295-5

73. Herz J, Kowal RC, Goldstein JL, Brown MS. Proteolytic processing of the 600 kd low density lipoprotein receptor‐related protein (LRP) occurs in a trans‐Golgi compartment. The EMBO Journal 1990; 9(6): 1769–1776. doi: 10.1002/j.1460-2075.1990.tb08301.x

74. Ritchie K, Touchon J. Heterogeneity in senile dementia of the Alzheimer type: Individual differences, progressive deterioration or clinical sub-types? Journal of Clinical Epidemiology 1992; 45(12): 1391–1398. doi: 10.1016/0895-4356(92)90201-w

75. Murray ME, Graff-Radford NR, Ross OA, et al. Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: A retrospective study. The Lancet Neurology 2011; 10(9): 785–796. doi: 10.1016/S1474-4422(11)70156-9

76. Weintraub S, Wicklund AH, Salmon DP. The neuropsychological profile of Alzheimer disease. Cold Spring Harbor Perspectives in Medicine 2012; 2(4): a006171. doi: 10.1101/cshperspect.a006171

77. Slattery CF, Crutch SJ, Schott JM. Phenotypical variation in Alzheimer’s disease: Insights from posterior cortical atrophy. Practical Neurology 2015; 15(1): 2–4. doi: 10.1136/practneurol-2014-000955

78. Beffert U, Aumont N, Dea D, et al. Beta‐amyloid peptides increase the binding and internalization of apolipoprotein E to hippocampal neurons. Journal of Neurochemistry 1998; 70(4): 1458–1466. doi: 10.1046/j.1471-4159.1998.70041458.x

79. Hone E, Martins IJ, Jeoung M, et al. Alzheimer’s disease amyloid-beta peptide modulates apolipoprotein E isoform specific receptor binding. Journal of Alzheimer’s Disease 2005; 7(4): 303–314. doi: 10.3233/jad-2005-7406

80. LaDu MJ, Falduto MT, Manelli AM, et al. Isoform-specific binding of apolipoprotein E to beta-amyloid. Journal of Biological Chemistry 1994; 269(38): 23403–23406.

81. McDonald C. Clinical heterogeneity in senile dementia. The British Journal of Psychiatry 1969; 115(520): 267–271. doi: 10.1192/bjp.115.520.267

82. Clinical, imaging, and pathological heterogeneity of the Alzheimer’s disease syndrome. Alzheimer’s Research & Therapy 2013; 5(1): 1–4. doi: 10.1186/alzrt155

83. Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimer’s & Dementia 2012; 8(1): 1–13. doi: 10.1016/j.jalz.2011.10.007

84. Khachaturian ZS. Diagnosis of Alzheimer’s disease. Archives of Neurology 1985; 42(11): 1097–1105. doi: 10.1001/archneur.1985.04060100083029

85. Mirra SS, Heyman A, McKeel D, et al. The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 1991; 41(4): 479–486. doi: 10.1212/wnl.41.4.479

86. Kumar A, Dogra S. Neuropathology and therapeutic management of Alzheimer’s disease—An update. Drugs of the Future 2008; 33(5): 433–446. doi: 10.1358/dof.2008.033.05.1192677

87. Hardy J. The amyloid hypothesis for Alzheimer’s disease: A critical reappraisal. Journal of Neurochemistry 2009; 110(4): 1129–1134. doi: 10.1111/j.1471-4159.2009.06181.x

88. Dal Prà I, Chiarini A, Gui L, et al. Do astrocytes collaborate with neurons in spreading the “infectious” aβ and Tau drivers of Alzheimer’s disease? The Neuroscientist 2015; 21(1): 9–29. doi: 10.1177/1073858414529828

89. Rosenmann H. Immunotherapy for targeting tau pathology in Alzheimer’s disease and tauopathies. Current Alzheimer Research 2013; 10(3): 217–228. doi: 10.2174/1567205011310030001

90. Mohsina FP, Faheem IP, Priya S, Husain SMA. Evaluation of anti diabetic activity of ichnocarpus frutescens L. International Journal of Advances in Pharmacy and Biotechnology 2018; 4(2): 1–2. doi: 10.38111/ijapb.20180402001

91. Roth AD, Ramírez G, Alarcón R, Von Bernhardi R. Oligodendrocytes damage in Alzheimer’s disease: Beta amyloid toxicity and inflammation. Biological Research 2005; 38(4): 381–387. doi: 10.4067/s0716-97602005000400011

92. Mohsina FP, Quazi A, Faheem IP, et al. Botanical, ethnopharmacological, phytochemical & pharmacological standards of plant ichnocarpus frutescens. Research & Review: Drugs and Drugs Development 2022; 4(1): 1–2. doi: 10.46610/RRDDD.2022.v04i01.001

93. Chaturvedi V, Goyal S, Mukim M, et al. A comprehensive review on Catharanthus roseus L. (G.) Don: Clinical pharmacology, ethnopharmacology and phytochemistry. Journal of Pharmacological Research and Developments 2022; 4(2): 17–36. doi: 10.46610/JPRD.2022.v04i02.003

94. Xu Y, Yan J, Zhou P, et al. Neurotransmitter receptors and cognitive dysfunction in Alzheimer’s disease and Parkinson’s disease. Progress in Neurobiology 2012; 97(1): 1–13. doi: 10.1016/j.pneurobio.2012.02.002

95. Selkoe DJ. Alzheimer’s disease: Genes, proteins, and therapy. Physiological Reviews 2001; 81(2): 741–766. doi: 10.1152/physrev.2001.81.2.741

96. Wenk GL. Neuropathologic changes in Alzheimer’s disease. Journal of Clinical Psychiatry 2003; 64 (Suppl 9): 7–10.

97. Boncristiano S, Calhoun ME, Kelly PH, et al. Cholinergic changes in the APP23 transgenic mouse model of cerebral amyloidosis. Journal of Neuroscience 2002; 22(8): 3234–3243. doi: 10.1523/JNEUROSCI.22-08-03234.2002

98. Yasojima K, McGeer EG, McGeer PL. Relationship between beta amyloid peptide generating molecules and neprilysin in Alzheimer disease and normal brain. Brain Research 2001; 919(1): 115–121. doi: 10.1016/s0006-8993(01)03008-6

99. Braak H, Del Tredici K. Alzheimer’s pathogenesis: Is there neuron-to-neuron propagation? Acta Neuropathologica 2011; 121(5): 589–595. doi: 10.1007/s00401-011-0825-z

100. Tuppo EE, Arias HR. The role of inflammation in Alzheimer’s disease. The International Journal of Biochemistry & Cell Biology 2005; 37(2): 289–305. doi: 10.1016/j.biocel.2004.07.009

101. Schenk D, Barbour R, Dunn W, et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999; 400(6740): 173–177. doi: 10.1038/22124

102. Zlokovic BV. Clearing amyloid through the blood-brain barrier. Journal of Neurochemistry 2004; 89(4): 807–811. doi: 10.1111/j.1471-4159.2004.02385.x

103. Sagare A, Deane R, Bell RD, et al. Clearance of amyloid-beta by circulating lipoprotein receptors. Nature Medicine 2007; 13(9) :1029–1031. doi: 10.1038/nm1635

104. Yan SD, Bierhaus A, Nawroth PP, Stern DM. RAGE and Alzheimer’s disease: A progression factor for amyloid-β-induced cellular perturbation? Journal of Alzheimer’s Disease 2009; 16(4): 833–843. doi: 10.3233/JAD-2009-1030

105. Shinde MU, Patwekar M, Patwekar F, et al. Nanomaterials: A potential hope for life sciences from bench to bedside. Journal of Nanomaterials 2022; 2022: 5968131. doi: 10.1155/2022/5968131

106. Chang WP, Huang X, Downs D, et al. β-Secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice. The FASEB Journal 2011; 25(2): 775–784. doi: 10.1096/fj.10-167213

107. Janusz M, Zablocka A. Colostral proline-rich polypeptides-immunoregulatory properties and prospects of therapeutic use in Alzheimer’s disease. Current Alzheimer Research 2010; 7(4): 323–333. doi: 10.2174/156720510791162377

108. Jacobsen JS, Comery TA, Martone RL, et al. Enhanced clearance of Abeta in brain by sustaining the plasmin proteolysis cascade. Proceedings of the National Academy of Sciences 2008; 105(25): 8754–8759. doi: 10.1073/pnas.0710823105

109. Saito T, Iwata N, Tsubuki S, et al. Somatostatin regulates brain amyloid β peptide Aβ42 through modulation of proteolytic degradation. Nature Medicine 2005; 11(4): 434–439. doi: 10.1038/nm1206

110. Scarpini E, Bruno G, Zappalà G, et al. Cessation versus continuation of galantamine treatment after 12 months of therapy in patients with Alzheimer’s disease: A randomized, double blind, placebo controlled withdrawal trial. Journal of Alzheimer’s Disease 2011; 26(2): 211–220. doi: 10.3233/JAD-2011-110134

111. Hock C, Nitsch RM. Clinical observations with AN-1792 using TAPIR analyses. Neurodegenerative Diseases 2005; 2(5): 273–276. doi: 10.1159/000090368

112. Nicoll JAR, Wilkinson D, Holmes C, et al. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: A case report. Nature Medicine 2003; 9(4): 448–452. doi: 10.1038/nm840

113. Buée L, Bussière T, Buée-Scherrer V, et al. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Research Reviews 2000; 33(1): 95–130. doi: 10.1016/s0165-0173(00)00019-9

114. Engel T, Goñi‐Oliver P, Lucas JJ, et al. Chronic lithium administration to FTDP‐17 tau and GSK‐3beta overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre‐formed neurofibrillary tangles do not revert. Journal of Neurochemistry 2006; 99(6): 1445–1455. doi: 10.1111/j.1471-4159.2006.04139.x

115. Zhang B, Maiti A, Shively S, et al. Microtubule-binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a tauopathy model. Proceedings of the National Academy of Sciences 2005; 102(1): 227–231. doi: 10.1073/pnas.0406361102

116. Pange SS, Patwekar M, Patwekar F, et al. A potential notion on Alzheimer’s disease: Nanotechnology as an alternative solution. Journal of Nanomaterials 2022; 2022(2): 6910811. doi: 10.1155/2022/6910811

117. Chai X, Wu S, Murray TK, et al. Passive immunization with anti-tau antibodies in two transgenic models: Reduction of tau pathology and delay of disease progression. Journal of Biological Chemistry 2011; 286(39): 34457–34467. doi: 10.1074/jbc.M111.229633

118. Butterfield DA, Pocernich CB. The glutamatergic system and Alzheimer’s disease: Therapeutic implications. CNS Drugs 2003; 17(9): 641–652. doi: 10.2165/00023210-200317090-00004

119. Miguel-Hidalgo JJ, Paul IA, Wanzo V, Banerjee PK. Memantine prevents cognitive impairment and reduces Bcl-2 and caspase 8 immunoreactivity in rats injected with amyloid β1-40. European Journal of Pharmacology 2012; 692(1-3): 38–45. doi: 10.1016/j.ejphar.2012.07.032

120. Hellweg R, Wirth Y, Janetzky W, Hartmann S. Efficacy of memantine in delaying clinical worsening in Alzheimer’s disease (AD): Responder analyses of nine clinical trials with patients with moderate to severe AD. International Journal of Geriatric Psychiatry 2012; 27(6): 651–656. doi: 10.1002/gps.2766

121. Ni R, Marutle A, Nordberg A. Modulation of α7 nicotinic acetylcholine receptor and fibrillar amyloid-β interactions in Alzheimer’s disease brain. Journal of Alzheimer’s Disease 2013; 33(3): 841–851. doi: 10.3233/JAD-2012-121447

122. Bösel J, Gandor F, Harms C, et al. Neuroprotective effects of atorvastatin against glutamate‐induced excitotoxicity in primary cortical neurones. Journal of Neurochemistry 2005; 92(6): 1386–1398. doi: 10.1111/j.1471-4159.2004.02980.x

123. Yue Y, Hu L, Tian QJ, et al. Effects of long‐term, low‐dose sex hormone replacement therapy on hippocampus and cognition of postmenopausal women of different apoE genotypes. Acta Pharmacologica Sinica 2007; 28(8): 1129–1135. doi: 10.1111/j.1745-7254.2007.00618.x

124. Kumar A, Singh A, Ekavali. A review on Alzheimer’s disease pathophysiology and its management: An update. Pharmacological Reports 2015; 67(2): 195–203. doi: 10.1016/j.pharep.2014.09.004

125. Vatansever S, Schlessinger A, Wacker D, et al. Artificial intelligence and machine learning‐aided drug discovery in central nervous system diseases: State‐of‐the‐arts and future directions. Medicinal Research Reviews 2021; 41(3): 1427–1473. doi: 10.1002/med.21764

126. Krishnamurthy N, Grimshaw AA, Axson SA, et al. Drug repurposing: A systematic review on root causes, barriers and facilitators. BMC Health Services Research 2022; 22(1): 970. doi: 10.1186/s12913-022-08272-z

127. Diaz V, Rodríguez G. Machine learning for detection of cognitive impairment. Acta Polytechnica Hungarica 2022; 19(5): 196–213.

128. Arrué L, Cigna-Méndez A, Barbosa T, et al. New drug design avenues targeting Alzheimer’s disease by pharmacoinformatics-aided tools. Pharmaceutics 2022; 14(9): 1914. doi: 10.3390/pharmaceutics14091914

129. Narayanan RR, Durga N, Nagalakshmi S. Impact of artificial intelligence (AI) on drug discovery and product development. Indian Journal of Pharmaceutical Education and Research 2022; 56(3): S387–S397.



  • There are currently no refbacks.

License URL: