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Review

Therapeutic Promise and Biotechnological Prospects of Dendroaspis polylepis Venom Proteins: Mambalgins, Fasciculins, and Dendrotoxins

by
Tomasz Kowalczyk
1,
Martyna Muskała
2,
Janusz Piekarski
3,
Maciej Kowalski
2,
Marek Staszewski
4,
Belma Konuklugil
5,6,
Patricia Rijo
7,8 and
Przemysław Sitarek
9,*
1
Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
2
Students Research Group, Department of Medical Biology, Medical University of Lodz, 90-151 Lodz, Poland
3
Department of Surgical Oncology, Medical University of Lodz, Pomorska 251, 93-513 Lodz, Poland
4
Department of Synthesis and Technology of Drugs, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland
5
Department of Pharmacognosy, Faculty of Pharmacy, Ankara University, Ankara 06560, Turkey
6
Department of Pharmacognosy, Faculty of Pharmacy, Lokman Hekim University, Ankara 06510, Turkey
7
CBIOS-Research Center for Biosciences & Health Technologies, Universidade Lusófona de Humanidades e Tecnologias, 1749-024 Lisbon, Portugal
8
iMed.ULisboa-Research Institute for Medicines, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal
9
Department of Medical Biology, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(20), 9895; https://doi.org/10.3390/ijms26209895 (registering DOI)
Submission received: 3 September 2025 / Revised: 30 September 2025 / Accepted: 7 October 2025 / Published: 11 October 2025
(This article belongs to the Special Issue Venom Research)
Versions Notes

Abstract

Animal toxins contain various bioactive peptides and proteins which have evolved to interact in specific ways. As such, they are a good starting point for developing new drugs and vaccines. This paper examines three natural neurotoxins derived from the black mamba (Dendroaspis polylepis), which show significant pharmacological potential: mambalgins, fasciculins and dendrotoxins. All three may be of value in the treatment of pain, cancer and neurodegenerative disease. Mambalgins provide similar pain relief to opioids but without the risk of addiction; they act by selectively blocking acid-sensitive ion channels (ASICs), especially ASIC1a. Thanks to this inhibitory activity they also demonstrate selective activity against glioblastoma, melanoma and leukemia cells as innovative anticancer drugs. Fasciculins are very strong inhibitors of acetylcholinesterase (AChE) and hence offer promise in multi-target drugs and as treatments for treating Alzheimer’s disease. Dendrotoxins such as DTX-K and DTX-I are able to modulate neuronal excitability and synaptic transmission by blocking voltage-gated potassium channels (Kv1.1, Kv1.2, Kv1.6); both have been shown to be effective against cancer cells, and to influence the cardiovascular, immune, and digestive systems. Recent advances in recombinant biotechnology and protein engineering have allowed their safe production with increased therapeutic value. The review examines the translational potential of D. polylepis venom proteins and highlights the need for additional preclinical research on bioactive molecules of toxin origin.
Keywords: black mamba; mambalgin; dendrotoxin; fasciculin; ASIC1a; Kv1 channels; recombinant toxins; neurotoxins; venom-derived therapeutics; anticancer effect black mamba; mambalgin; dendrotoxin; fasciculin; ASIC1a; Kv1 channels; recombinant toxins; neurotoxins; venom-derived therapeutics; anticancer effect

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MDPI and ACS Style

Kowalczyk, T.; Muskała, M.; Piekarski, J.; Kowalski, M.; Staszewski, M.; Konuklugil, B.; Rijo, P.; Sitarek, P. Therapeutic Promise and Biotechnological Prospects of Dendroaspis polylepis Venom Proteins: Mambalgins, Fasciculins, and Dendrotoxins. Int. J. Mol. Sci. 2025, 26, 9895. https://doi.org/10.3390/ijms26209895

AMA Style

Kowalczyk T, Muskała M, Piekarski J, Kowalski M, Staszewski M, Konuklugil B, Rijo P, Sitarek P. Therapeutic Promise and Biotechnological Prospects of Dendroaspis polylepis Venom Proteins: Mambalgins, Fasciculins, and Dendrotoxins. International Journal of Molecular Sciences. 2025; 26(20):9895. https://doi.org/10.3390/ijms26209895

Chicago/Turabian Style

Kowalczyk, Tomasz, Martyna Muskała, Janusz Piekarski, Maciej Kowalski, Marek Staszewski, Belma Konuklugil, Patricia Rijo, and Przemysław Sitarek. 2025. "Therapeutic Promise and Biotechnological Prospects of Dendroaspis polylepis Venom Proteins: Mambalgins, Fasciculins, and Dendrotoxins" International Journal of Molecular Sciences 26, no. 20: 9895. https://doi.org/10.3390/ijms26209895

APA Style

Kowalczyk, T., Muskała, M., Piekarski, J., Kowalski, M., Staszewski, M., Konuklugil, B., Rijo, P., & Sitarek, P. (2025). Therapeutic Promise and Biotechnological Prospects of Dendroaspis polylepis Venom Proteins: Mambalgins, Fasciculins, and Dendrotoxins. International Journal of Molecular Sciences, 26(20), 9895. https://doi.org/10.3390/ijms26209895

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