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Review

Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives

1
Dompé Farmaceutici SpA, 80131 Napoli, Italy
2
Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 Coppito, Italy
3
Paolo Procacci Foundation, 00193 Rome, Italy
4
Dompé Farmaceutici SpA, 67100 L’Aquila, Italy
*
Author to whom correspondence should be addressed.
These authors equally contributed to the manuscript.
Academic Editor: Anand Rotte
Biomedicines 2021, 9(4), 399; https://doi.org/10.3390/biomedicines9040399
Received: 8 March 2021 / Revised: 30 March 2021 / Accepted: 1 April 2021 / Published: 7 April 2021
(This article belongs to the Special Issue Neuropathic Pain: Therapy and Mechanisms)
The complement system is a key component of innate immunity since it plays a critical role in inflammation and defense against common pathogens. However, an inappropriate activation of the complement system is involved in numerous disorders, including peripheral neuropathies. Current strategies for neuropathy-related pain fail to achieve adequate pain relief, and although several therapies are used to alleviate symptoms, approved disease-modifying treatments are unavailable. This urgent medical need is driving the development of therapeutic agents for this condition, and special emphasis is given to complement-targeting approaches. Recent evidence has underscored the importance of complement component C5a and its receptor C5aR1 in inflammatory and neuropathic pain, indicating that C5a/C5aR1 axis activation triggers a cascade of events involved in pathophysiology of peripheral neuropathy and painful neuro-inflammatory states. However, the underlying pathophysiological mechanisms of this signaling in peripheral neuropathy are not fully known. Here, we provide an overview of complement pathways and major components associated with dysregulated complement activation in peripheral neuropathy, and of drugs under development targeting the C5 system. C5/C5aR1 axis modulators could represent a new strategy to treat complement-related peripheral neuropathies. Specifically, we describe novel C5aR allosteric modulators, which may potentially become new tools in the therapeutic armory against neuropathic pain. View Full-Text
Keywords: complement system; C5a/C5aR axis; C5a receptor1; peripheral neuropathy; pain; C5aR inhibitor; allosteric modulator complement system; C5a/C5aR axis; C5a receptor1; peripheral neuropathy; pain; C5aR inhibitor; allosteric modulator
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MDPI and ACS Style

Giorgio, C.; Zippoli, M.; Cocchiaro, P.; Castelli, V.; Varrassi, G.; Aramini, A.; Allegretti, M.; Brandolini, L.; Cesta, M.C. Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives. Biomedicines 2021, 9, 399. https://doi.org/10.3390/biomedicines9040399

AMA Style

Giorgio C, Zippoli M, Cocchiaro P, Castelli V, Varrassi G, Aramini A, Allegretti M, Brandolini L, Cesta MC. Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives. Biomedicines. 2021; 9(4):399. https://doi.org/10.3390/biomedicines9040399

Chicago/Turabian Style

Giorgio, Cristina, Mara Zippoli, Pasquale Cocchiaro, Vanessa Castelli, Giustino Varrassi, Andrea Aramini, Marcello Allegretti, Laura Brandolini, and Maria Candida Cesta. 2021. "Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives" Biomedicines 9, no. 4: 399. https://doi.org/10.3390/biomedicines9040399

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