Misfolding and accumulation of amyloid-β (Aβ)
to form
senile plaques are the main neuropathological signatures of Alzheimer’s
disease (AD). Decreasing Aβ production, inhibiting Aβ
aggregation, and clearing Aβ plaques are thus considered an
important strategy for AD treatment. However, numerous drugs cannot
enter the AD clinical trials due to unsatisfactory biocompatibility,
poor blood–brain barrier penetration, little biomarker impact,
and/or low therapeutic indicators. Here, a pair of chiral aspartic
acid-modified 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine
(l- and d-Asp-DPPE) are prepared to build stabilized
chiral liposomes. We find that both l- and d-liposomes
are able to rescue Aβ aggregation-induced apoptosis, oxidative
stress, and calcium homeostasis, in which the effect of d-liposomes is more obvious than that of l-ones. Furthermore,
in AD model mice (APPswe/PS1d9 double-transgenic mice), chiral liposomes
not only show biosafety but also strongly improve cognitive deficits
and reduce Aβ deposition in the brain. Our results suggest that
chiral liposomes, particularly, d-liposomes, could be a potential
therapeutic approach for AD treatment. This study opens new horizons
by showing that liposomes will be used for drug development in addition
to delivery and targeting functions.
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