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BMC Neurology
Published in: BMC Neurology 1/2017

Open Access 01-12-2017 | Debate

Can brain impermeable BACE1 inhibitors serve as anti-CAA medicine?

Authors: Jian-Ming Li, Li-Ling Huang, Fei Liu, Bei-Sha Tang, Xiao-Xin Yan

Published in: BMC Neurology | Issue 1/2017

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Abstract

Background

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of ß-amyloid peptides (Aß) in and surrounding the wall of microvasculature in the central nervous system, together with parenchymal amyloid plaques collectively referred to as cerebral amyloidosis, which occurs in the brain commonly among the elderly and more frequently in patients with Alzheimer’s disease (AD). CAA is associated with vascular injury and may cause devastating neurological outcomes. No therapeutic approach is available for this lesion to date.

Main body

ß-Secretase 1 (BACE1) is the enzyme initiating Aß production. Brain permeable BACE1 inhibitors targeting primarily at the parenchymal plaque pathology are currently evaluated in clinical trials. This article presents findings in support of a role of BACE1 elevation in the development of CAA, in addition to plaque pathogenesis. The rationale, feasibility, benefit and strategic issues for developing BACE1 inhibitors against CAA are discussed. Brain impermeable compounds are considered preferable as they might exhibit sufficient anti-CAA efficacy without causing significant neuronal/synaptic side effects.

Conclusion

Early pharmacological intervention to the pathogenesis of CAA is expected to provide significant protection for cerebral vascular health and hence brain health. Brain impermeable BACE1 inhibitors should be optimized and tested as potential anti-CAA therapeutics.
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Metadata
Title
Can brain impermeable BACE1 inhibitors serve as anti-CAA medicine?
Authors
Jian-Ming Li
Li-Ling Huang
Fei Liu
Bei-Sha Tang
Xiao-Xin Yan
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2017
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-017-0942-y

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