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Freq.: Quarterly

eISSN: 2251-7308 
pISSN: 2228-5881 

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Adv Pharm Bull. 2023;13(4): 688-700. doi: 10.34172/apb.2023.071
PMID: 38022801        PMCID: PMC10676556

Review Article

Role of GSK-3β Inhibitors: New Promises and Opportunities for Alzheimer’s Disease

Suggala Ramya Shri 1 ORCID, Suman Manandhar 1 ORCID, Yogendra Nayak 1 ORCID, K Sreedhara Ranganath Pai 1 * ORCID

Cited by CrossRef: 11

1- Pal C. Mitochondria-targeting by small molecules against Alzheimer's disease: A mechanistic perspective. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2025;1871(3):167617 [Crossref]
2- Liu Y, Ma X, Xu J, Wang X, Liu L, Ren X, Zhang C, Zhou S, Wang Y, Guo X, Yuan L. Dietary n-3 polyunsaturated fatty acids intervention ameliorates cognitive dysfunction in db/db mice by mitigating cortical insulin resistance, mitochondrial dysfunction, and energy metabolism impairment. Journal of Advanced Research. 2025; [Crossref]
3- Alshehri G, Al-kuraishy H, Waheed H, Al-Gareeb A, Faheem S, Alexiou A, Papadakis M, El-Saber Batiha G. Tirzepatide: a novel therapeutic approach for Alzheimer’s disease. Metab Brain Dis. 2025;40(5) [Crossref]
4- Shri S, Nayak Y, Ranganath Pai S. Molecular docking studies and molecular dynamic simulation analysis: To identify novel ATP-competitive inhibition of Glycogen synthase kinase-3β for Alzheimer’s disease. F1000Res. 2025;13:773 [Crossref]
5- Jitendra Joshi N, Raja Sekhar Reddy A. Navigating the GSK-3β inhibitors as versatile multi-target drug ligands in Alzheimer’s disease intervention – A comprehensive review. Results in Chemistry. 2024;7:101500 [Crossref]
6- Shri S, Nayak Y, Ranganath Pai S. Molecular docking studies and molecular dynamic simulation analysis: To identify novel ATP-competitive inhibition of Glycogen synthase kinase-3β for Alzheimer’s disease. F1000Res. 2024;13:773 [Crossref]
7- Thawabteh A, Ghanem A, AbuMadi S, Thaher D, Jaghama W, Karaman D, Karaman R. Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease. Molecules. 2024;29(21):5131 [Crossref]
8- Joshi N, Alavala R. Identification of novel ligands against GSK-3β: Molecular docking, ADMET filtering, MD simulations, MM-GBSA studies, and DFT analysis. Computational Biology and Chemistry. 2025;118:108478 [Crossref]
9- Saadh M, Hussein W, Alfarttoosi K, Bishoyi A, Roopashree R, Kundlas M, Chennakesavulu K, Kubaev A, Taher W, Alwan M, Jawad M, Ali Al-Nuaimi A, Farhood B. Identification of Phytochemicals as Promising GSK-3β Inhibitors for Cancer Therapeutic Potential Through Virtual Screening, Molecular Docking, MD Simulation and MM-PBSA Calculation. J Comput Biophys Chem. 2026;25(03):485 [Crossref]
10- Xun Q, Zhang J, Feng L, Ma Y, Li Y, Shi X. Identification of a novel pyrrolo[2,3- b ]pyridine compound as a potent glycogen synthase kinase 3β inhibitor for treating Alzheimer’s disease . Journal of Enzyme Inhibition and Medicinal Chemistry. 2025;40(1) [Crossref]
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14- Baumgartner T, Silva‐Pérez M, Haghighijoo Z, Dvorak N, Singh A, Goode N, Singh J, Grebenkova B, Marosi M, Di Re J, Koff L, Wijitrmektong W, Bala M, Liao H, Lijffijt M, Szafran A, Bolt M, Mancini M, Cuny G, Chow D, Limon A, Chin J, Laezza F. Inhibition of the GSK3β/Nav1.6 complex suppresses early‐stage Alzheimer's hyperexcitability. Alzheimer's & Dementia. 2025;21(7) [Crossref]
15- Shri S, Nayak Y, Ranganath Pai S. Molecular docking studies and molecular dynamic simulation analysis: To identify novel ATP-competitive inhibition of Glycogen synthase kinase-3β for Alzheimer’s disease. F1000Res. 2024;13:773 [Crossref]
16- Smail S, Kheder A, Mustafa H, Abdulqadir S, Jalal K, Yashooa R, Ghayour M, Abdolmaleki A, Shekha M. Kenpaullone attenuates amyloid-beta deposition and neuroinflammation, improving memory in a 5XFAD mouse model of Alzheimer’s disease. Neurological Research. 2025;:1 [Crossref]
17- Rekha A, Afzal M, Babu M, Menon S, Nathiya D, Supriya S, Mishra S, Gupta S, Goyal K, Rana M, Ali H, Imran M. GSK-3β dysregulation in aging: Implications for tau pathology and Alzheimer's disease progression. Molecular and Cellular Neuroscience. 2025;133:104005 [Crossref]
18- Góral I, Wichur T, Sługocka E, Godyń J, Szałaj N, Zaręba P, Głuch-Lutwin M, Mordyl B, Panek D, Więckowska A. Connecting GSK-3β Inhibitory Activity with IKK-β or ROCK-1 Inhibition to Target Tau Aggregation and Neuroinflammation in Alzheimer’s Disease—Discovery, In Vitro and In Cellulo Activity of Thiazole-Based Inhibitors. Molecules. 2024;29(11):2616 [Crossref]
19- El‐Kadi R, AbdelKader N, Zaki H, Kamel A. Influence of β‐catenin signaling on neurogenesis in neuropsychiatric disorders: Anxiety and depression. Drug Development Research. 2024;85(1) [Crossref]
20- Alshahrani S, Al-kuraishy H, Al-Gareeb A, Albuhadily A, Fawzy M, Kadasah S, Alruwaili M, Papadakis M, Alexiou A, El-Saber Batiha G. Berberine's paradox in Neurodegeneration: Therapeutic promise and safety challenges in Parkinson's disease. Neuropharmacology. 2025;278:110555 [Crossref]
21- Bayraktar G, Alptüzün V. Recent Molecular Targets and their Ligands for the Treatment of Alzheimer Disease. CTMC. 2024;24(28):2447 [Crossref]
22- Turkistani A, Al-kuraishy H, Al-Gareeb A, Albuhadily A, Alexiou A, Papadakis M, Elfiky M, Saad H, Batiha G. Therapeutic Potential Effect of Glycogen Synthase Kinase 3 Beta (GSK-3β) Inhibitors in Parkinson Disease: Exploring an Overlooked Avenue. Mol Neurobiol. 2024;61(9):7092 [Crossref]
23- Ziętal K, Mirowska-Guzel D, Nowaczyk A, Blecharz-Klin K. Cnicus benedictus: Folk Medicinal Uses, Biological Activities, and In Silico Screening of Main Phytochemical Constituents. Planta Med. 2024;90(13):976 [Crossref]
24- Dunlap N, Friedland R, Cai L. Alzheimer's disease and low-dose radiation therapy: A new hope. Radiation Medicine and Protection. 2024;5(1):1 [Crossref]
25- Asl F, Malverdi N, Mojahedian F, Baziyar P, Nabi-Afjadi M. Discovery of effective GSK-3β inhibitors as therapeutic potential against Alzheimer's disease: A computational drug design insight. International Journal of Biological Macromolecules. 2025;306:141273 [Crossref]
26- Ansari M, Sahu S, Singh T, Singh S, Kaur P. Evolving significance of kinase inhibitors in the management of Alzheimer's disease. European Journal of Pharmacology. 2024;979:176816 [Crossref]
27- Antonioni A, Martorana A, Santarnecchi E, Hampel H, Koch G. The neurobiological foundation of effective repetitive transcranial magnetic brain stimulation in Alzheimer's disease. Alzheimer's & Dementia. 2025;21(6) [Crossref]
28- Yang C, Liu Y, Lin T, Chang K, Hsieh-Li H. Fermented Soybean Pulp Alleviates Disease Progression of 5×FAD Model Mice. Mol Neurobiol. 2025; [Crossref]
29- Sharma A, Mannan A, Singh T. Unraveling novel mechanisms of ATP-Binding cassette (ABC) transporter in insulin Resistance-induced amyloidogenesis. Metab Brain Dis. 2025;40(5) [Crossref]
30- Sai Varshini M, Aishwarya Reddy R, Thaggikuppe Krishnamurthy P. Unlocking hope: GSK-3 inhibitors and Wnt pathway activation in Alzheimer’s therapy. Journal of Drug Targeting. 2024;32(8):909 [Crossref]