Blood-brain barrier penetrating neprilysin degrades monomeric amyloid-beta in a mouse model of Alzheimer's disease.

ABSTRACT:

Background

Aggregation of the amyloid-β (Aβ) peptide in the brain is one of the key pathological events in Alzheimer's disease (AD). Reducing Aβ levels in the brain by enhancing its degradation is one possible strategy to develop new therapies for AD. Neprilysin (NEP) is a membrane-bound metallopeptidase and one of the major Aβ-degrading enzymes. The secreted soluble form of NEP (sNEP) has been previously suggested as a potential protein-therapy degrading Aβ in AD. However, similar to other large molecules, peripherally administered sNEP is unable to reach the brain due to the presence of the blood-brain barrier (BBB).

Methods

To provide transcytosis across the BBB, we recombinantly fused the TfR binding moiety (scFv8D3) to either sNEP or a previously described variant of NE

SUBMITTER: Rofo F 

PROVIDER: S-EPMC9720954 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature