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://www.rjppd.org/AbstractView.aspx?PID=2026-18-2-13
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