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Targeting complement in neurodegeneration: challenges, risks, and strategies

Zelek, Wioleta M. and Morgan, B. Paul ORCID: 2022. Targeting complement in neurodegeneration: challenges, risks, and strategies. Trends in Pharmacological Sciences 43 (8) , pp. 615-628. 10.1016/

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For most neurodegenerative diseases (NDDs), therapeutic options are limited, providing symptomatic benefit but not impacting disease progression; new treatments addressing critical effectors in the disease process are needed. Evidence implicating complement in NDDs has accumulated over the past two decades, establishing complement dysregulation as a driver of pathology and a novel target for therapy in these diseases. Over the same period, highly effective anticomplement drugs have been developed for therapy of complement dysregulation; however, their use to date has been restricted to rare systemic diseases. Current anticomplement drugs are not fit for purpose in most NDDs because they do not adequately access the central nervous system (CNS). Blood–brain barrier-penetrant anticomplement drugs, created either by modifying current drugs or by designing new drugs, could suppress complement dysregulation, neuroinflammation, and neurodegeneration to halt or slow disease progression. Inhibition of complement is not without risk; this might be particularly the case in the CNS and requires close attention.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: Attribution 4.0 International (CC BY 4.0)
Publisher: Cell Press
ISSN: 0165-6147
Date of First Compliant Deposit: 20 July 2022
Date of Acceptance: 9 February 2022
Last Modified: 06 May 2023 14:14

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