Somatostatin therapy, neprilysin activation, and amyloid beta reduction: A novel approach for Alzheimer's treatment - 20/07/25
, Ana Godec a, Alex Petrovic a, Aikaterini Chourlia a, Antonino Napoleone a, Stina Syvänen b, Fadi Rofo a, Greta Hultqvist a, ⁎ Abstract |
Introduction |
Neprilysin is the primary enzyme responsible for the degradation of amyloid beta (Aβ), with its levels regulated by the hormone somatostatin (SST).
Methods |
We have developed a novel treatment mechanism for Alzheimer’s disease (AD) by combining SST with a blood-brain barrier (BBB) transporter and a Fc fragment to extend its half-life. This treatment was tested in a murine AD model overexpressing amyloid precursor protein (APP) with the Arctic mutation in Aβ (APPArcSwe).
Results |
Our findings demonstrate a significant increase in neprilysin levels, which correlates with a reduction in various forms of Aβ, including membrane-bound and intracellular Aβ aggregates, as well as Aβ42 in insoluble aggregates.
Discussion |
These results suggest that neprilysin can effectively degrade Aβ with the Arctic mutation. Additionally, this treatment strategy successfully reduces both oligomeric and larger Aβ, aggregates, a challenge for other therapeutic approaches. This novel strategy holds promise as a potential therapeutic approach for AD.
El texto completo de este artículo está disponible en PDF.Graphical Abstract |
Highlights |
• | Decreased formation of oligomeric amyloid beta after somatostatin treatment. |
• | Evidence that neprilysin can also degrade arctic amyloid beta. |
• | Somatostatin enhances the activity of neprilysin, leading to reduced levels of small amyloid beta aggregates and insoluble amyloid beta. |
Keywords : Neprilysin, Somatostatin, SST, MME, Transferrin receptor, TfR, Blood brain barrier, BBB, Alzheimer’s disease, Degradation, Amyloid beta, Transport, Protein pharmaceutics, Biologicals, Aggregation, Oligomers, Hairpin, A11
Esquema
Vol 189
Artículo 118325- août 2025 Regresar al número
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