Summery of - Emerging therapeutic role of chondroitinase (ChABC) in neurological disorders and cancer

Document Type

Article

Abstract

Proteoglycans are essential biomacromolecules that participate in matrix structure and organization, cell proliferation and migration, and cell surface signal transduction. However, their roles in physiology, particularly in CNS remain incompletely deciphered. Numerous studies highlight the elevated levels of chondroitin sulphate proteoglycans (CSPGs) in various diseases like cancers, and neurological disorders like spinal cord injury (SCI), traumatic brain damage, and neurodegenerative diseases, and are mainly implicated to hinder tissue repair. In such a context, chondroitinase ABC (ChABC), a therapeutic enzyme, has shown immense hope to treat these diseases in several preclinical studies, primarily attributed to the digestion of the side chains of the proteoglycan chondroitin sulphate (CS) molecule. Despite extensive research, the progress in evolution of the concept of therapeutic targeting of proteoglycans is still in its infancy. This review thus provides fresh insights into the emerging therapeutic applications of ChABC in various diseases apart from SCI and the underlying mechanisms.

Conclusion

Proteoglycans (PGs) are essential biomacromolecules and mediate various important processes in cells. CSPGs also play a significant role in CNS. The levels of CSPGs are elevated in injury and other stressful conditions, and hinder recovery and repair. As a result, mounting evidence indicates that regulating inhibitory CSPG levels via a variety of methods, including ChABC therapy, is effective for spinal cord repair and regeneration. The relevance of ChABC as a therapeutic target is demonstrated by its usage in pre-clinical models of SCI, other neurodegenerative diseases, and some types of cancer. However, low productivity, route of administration, and post-translational modifications are the major limitations in the clinical translation of these molecules. Besides, proposing ChABC as a therapeutic molecule should be cautious as it can bear non-specific effects over normal functioning.

Since a proper cure is not available for all the above-discussed diseases, a search for novel therapies remains to be continued. Indeed, currently, there is limited proof that ChABC treatment can be successful as it is staged in animal studies. ECM being present in all tissues of the human body has a significant and complex role in any disease development which is not fully understood and seeks future research. Possibly, the findings will aid in the identification of a more effective strategy to deal with using ChABC for the same. Nonetheless, more studies on understanding the mechanism of action of the ChABC molecules and proteoglycans are needed to uncover its promising clinical applications.

Citation style:

Kumar, A., Biswas, A., Bojja, S. L., Kolathur, K. K., & Volety, S. Y. M. (2022). Emerging Therapeutic Role of Chondroitinase (ChABC) in Neurological Disorders and Cancer. Current Drug Therapy, 17(3), 160-170.

https://doi.org/10.2174/1574885517666220331151619

Publication Date

2022

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