Author(s): Navinkumar Malligarjunan, Subabala S, Sundaraleela K, Lavanya M, Srinithi P

Email(s): msnavink26@gmail.com

DOI: 10.52711/2321-5836.2026.00028   

Address: Navinkumar Malligarjunan1*, Subabala S2, Sundaraleela K2, Lavanya M2, Srinithi P2
1Department of Pharmaceutical Chemistry, BGS Golbal Institute of Pharmaceutical Sciences, Kengeri, Bengaluru, Karnataka, India.
2Vivekananda Pharmacy College, Salem, Tamil Nadu, India.
*Corresponding Author

Published In:   Volume - 18,      Issue - 2,     Year - 2026


ABSTRACT:
The mycobacterial enzyme KatG activates the prodrug INH, which produces reactive intermediates that prevent the formation since its introduction in 1952, isoniazid (INH), a first-line antitubercular medication, has been known for its strong and specific action against Mycobacterium TB. The mycobacterial enzyme KatG activates the prodrug INH, which produces reactive intermediates that prevent the formation of mycolic acid and inhibit InhA, ultimately causing bacterial cell death. Recent studies have demonstrated INH's potential utility in neuropharmacology in addition to its well-established antibacterial function. INH is a promising scaffold for creating neuroprotective derivatives since experimental research indicates that its hydrazide and pyridine moieties contribute to anti-inflammatory, antioxidant, and anti-apoptotic activities. Emerging preclinical evidence indicates that INH can modulate key pathways implicated in neurodegenerative diseases, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). INH has been shown to suppress monoamine oxidase-B (MAO-B) and BACE1, reduce neuroinflammation, and preserve synaptic structure in AD mouse models. In PD, INH’s interaction with pyridoxal-5-phosphate temporarily alters GABA synthesis, potentially restoring dopaminergic–GABAergic balance and reducing levodopa-induced dyskinesia, although clinical effects remain inconsistent. Several INH-based derivatives also display antioxidant activity, improved mitochondrial protection, and reduction of pathological protein aggregation in experimental models. Nonetheless, INH's simple structure, favorable pharmacokinetics, and modifiable hydrazide backbone make it an appealing starting point for multi-target drug development targeting neuroinflammation, oxidative stress, and protein misfolding—central mechanisms shared by major neurodegenerative diseases.


Cite this article:
Navinkumar Malligarjunan, Subabala S, Sundaraleela K, Lavanya M, Srinithi P. Repurposing Isoniazid: A Comprehensive Review of its Therapeutic Potential in Neurodegeneration. Research Journal of Pharmacology and Pharmacodynamics.2026;18(2):205-1. doi: 10.52711/2321-5836.2026.00028

Cite(Electronic):
Navinkumar Malligarjunan, Subabala S, Sundaraleela K, Lavanya M, Srinithi P. Repurposing Isoniazid: A Comprehensive Review of its Therapeutic Potential in Neurodegeneration. Research Journal of Pharmacology and Pharmacodynamics.2026;18(2):205-1. doi: 10.52711/2321-5836.2026.00028   Available on: https://rjppd.org/AbstractView.aspx?PID=2026-18-2-13


REFERENCE:
1.    Fernandes GFDS, Salgado HRN, Santos JLDS. Isoniazid: a review of characteristics, properties and analytical methods. 2017 Jul 4; 47(4): 298–308.
2.    O'Connor C, Patel P, Brady MF. Isoniazid. Treasure Island (FL): StatPearls Publishing; 2025 Jan.
3.    Joydeep P, Nasiruddi M, Ahmad KI, Ali KR, Hasan AS. Therapeutic effect of Nigella sativa oil in hepatotoxicity induced by isoniazid in rats. Apr–Jun 2019; 53(2).
4.    Jishnu S, Anjali C, Ramandeep S, Dinesh M. Isoniazid-historical development, metabolism associated toxicity and a perspective on its pharmacological improvement, 2024 Sep 19: 15: 1441147.
5.    Chen J, Guo N, Ruan Y, Mai Y, Liao W, Feng Y. Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice. 2023 Jan 19; 15:1105095. Perry TL, Wright JM, Hansen S, Thomas SMB, Allan BM, Baird PA. A double-blind clinical trial of isoniazid in Huntington disease. April 1982; 32(4):354.
6.    Gershanik OS, Luquin MR, Scipioni O, Obeso JA. Isoniazid therapy in Parkinson's disease. 1988;3(2):133–9.
7.    Santos DC, Henriques RR, Lopes Junior MAA, Farias AB, Nogueira TLC, Quimas JVF. Acylhydrazones as isoniazid derivatives with multi-target profiles for the treatment of Alzheimer's disease: radical scavenging, myeloperoxidase/ acetylcholinesterase inhibition and biometal chelation. 2020 May 15; 28(10): 115470.
8.    Volynets GP, Tukalo MA, Bdzhola VG, Derkach NM, Gumeniuk MI, Tarnavskiy SS, Yarmoluk SM. Novel isoniazid derivative as promising antituberculosis agent. 2020 Jul; 15(10):869–879.
9.    Gadhave DG, Sugandhi VV, Jha SK, Nangare SN, Gupta G, Singh SK. Neurodegenerative disorders: mechanisms of degeneration and therapeutic approaches with their clinical relevance. 2024; 99: 102357.
10.    Ghosh S. Breathing disorders in neurodegenerative diseases. 2022; 189:223–239.
11.    Muddapu VR, Dharshini SAP, Chakravarthy VS, Gromiha MM. Neurodegenerative disorders - is metabolic deficiency the root cause? 2020; 31: 14:213.
12.    Davenport F, Gallacher J, Kourtzi Z, Koychev I, Matthews PM, Oxtoby NP. Neurodegenerative disease of the brain: a survey of interdisciplinary approaches. 2023 Jan; 20(198): 20220406.
13.    Kharat S, Mali S, Korade G, Gaykar R. Navigating neurodegenerative disorders: a comprehensive review of current and emerging therapies for neurodegenerative disorders. 2024;8(1)
14.    Lamptey RNL, Chaulagai B, Trivedi R, Gothwal A, Layek B, Singh J.  A review of the commen neurodegenerative disorder: current therapeutic approaches and the potential role of nanotherapeutics. 2022; 23(3): 1851. 
15.    Toader C, Tataru CP, Munteanu O, Serban M, Covache-Busuioc RA, Ciurea AV. Decoding neurodegeneration: a review of molecular mechanisms and therapeutic advances in Alzheimer’s, Parkinson’s, and ALS. 2024; 25(23): 12613.
16.    Koszła O, Sobek P. Misfolding and aggregation in neurodegenerative diseases: protein quality control machinery as potential therapeutic clearance pathways. 2024.
17.    Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443(7113):787–795.
18.    Nixon RA. The role of autophagy in neurodegenerative disease. Nat Med. 2013; 19(8): 983–997.
19.    Singleton AB, Hardy J. The evolution of genetics: Alzheimer’s and Parkinson’s diseases. Neuron. 2016; 90(6): 1154–1163.
20.    Wilson DM, Cookson MR, Bosch VDL, Zetterberg H, Holtzman DM, Dewachter I. Hallmarks of neurodegenerative diseases. 2023; 186(4): 693–714.
21.    Chao G, Jingwen J, Yuyan T, Shengdi C. Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets, 2023 sep 22; 8(1):359
22.    Zhu X, Yu J, Lai X, Wang X, Deng J, Long Y. Global burden of Alzheimer's disease and other dementias in adults aged 65 years and older, 1991–2021: population-based study. 2025 Jul 1; 13: 1585711.
23.    Wang S, Jiang Y, Yang A, Meng F, Zhang J. The expanding burden of neurodegenerative diseases: an unmet medical and social need. 2024 Nov 4;16(5):2937–2952.
24.    Luo Y, Qiao L, Li M, Wen X, Zhang W, Li X. Global, regional, national epidemiology and trends of Parkinson's disease from 1990 to 2021: findings from the Global Burden of Disease Study 2021. 2025 Jan 10; 16:1498756.
25.    Su D, Cui Y, He C, Yin P, Bai R, Zhu J. Projections for prevalence of Parkinson's disease and its driving factors in 195 countries and territories to 2050: modelling study of Global Burden of Disease Study 2021. 2025 Mar 5;388: e080952.
26.    Wei CJ, Lei B, Musser JM, Tu S-C. Isoniazid activation defects in recombinant Mycobacterium tuberculosis catalase-peroxidase (KatG) mutants evident in InhA inhibitor production. 2003 Feb;47(2):670–675.
27.    Argyrou A, Vetting MW, Blanchard JS. New insight into the mechanism of action of and resistance to isoniazid. 2007 Jul 18;129(31):9582–9583.
28.    Vilchèze C, Jacobs WR Jr. The mechanism of isoniazid killing: clarity through the scope of genetics. 2007; 61:35–50.
29.    Timmins GS, Deretic V. Mechanisms of action of isoniazid. 2006 Dec;62(5):1220–7.
30.    Brunton. L.L, Chabner. B.A, Knollmann. B.C. Goodman and Gilman’s The Pharmacological Basis of Therapeutics.
31.    Pahlavani E, Kargar H, Sepehri Rad N.  A study on antitubercular and antimicrobial activity of isoniazid derivative. 2015;17(7).
32.    Badrinath M, Chen RJ, John S. Isoniazid toxicity. Treasure Island (FL): StatPearls; 2025 Jan.
33.    Çelik H, Kucukler S, Çomaklı S, Caglayan C, Özdemir S, Yardım A. Neuroprotective effect of chrysin on isoniazid-induced neurotoxicity via suppression of oxidative stress, inflammation and apoptosis in rats. Neurotoxicology. 2020 Dec; 81:197–208.
34.    Chen J, Guo N, Ruan Y, Mai Y, Liao W, Feng Y. Isoniazid improves cognitive performance, clears Aβ plaques, and protects dendritic synapses in APP/PS1 transgenic mice. Front Aging Neurosci. 2023 Jan 19;15:Article 1105095.
35.    Hallett M, Lindsey JW, Adelstein BD, Riley PO. Controlled trial of isoniazid therapy for severe postural cerebellar tremor in multiple sclerosis. 1985 Sep;35(9):1374.
36.    Bartolić M, Matošević A, Maraković N, Bušić V, Roca S, Vikić-Topić D. Evaluation of hydrazone and N-acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde as potential drugs against Alzheimer’s disease. J Enzyme Inhib Med Chem. 2024;39(1).
37.    Gershanik OS, Luquin MR, Scipioni O, Obeso JA. Isoniazid therapy in Parkinson's disease. Mov Disord. 1988;3(2):133–9.
38.    Sekar PKC, Thomas SM. An overview of the role of monoamine oxidase-B in Parkinson’s disease: implications for neurodegeneration and therapy. Explor Neuroprot Ther. 2024; 4:308–318.
39.    Peedikayil AT, Lee J, Abdelgawad MA, Ghoneim M, Shaker ME, Selim S, Kumar S. Inhibitions of monoamine oxidases by ferulic acid hydrazide derivatives: synthesis, biochemistry, and computational evaluation. Appl Biol Chem. 2023 Oct 5.
40.    Santos DC, Henriques RR, Lopes Junior MAA, Farias AB, Nogueira TLC, Quimas JVF. Acylhydrazones as isoniazid derivatives with multi-target profiles for the treatment of Alzheimer’s disease: radical scavenging, myeloperoxidase/acetylcholinesterase inhibition and biometal chelation. Bioorg Med Chem. 2020 May 15;28(10):115470.
41.    Iraji A, Nikfar P, Montazer MN, Karimi M, Edraki N, Saeedi M, Mirfazli SS.  Synthesis, biological evaluation and molecular modeling studies of methyl indole-isoxazole carbohydrazide derivatives as multi-target anti-Alzheimer’s agents.  10 September 2024.
42.    Perry TL, Wright JM, Hansen S, MacLeod PM.  Isoniazid therapy of Huntington disease. 1979 Mar; 29(3):370-5.




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