Neuroscience

Nanotechnology

Enzyme

Combinatorial chemistry

Central nervous system

Stereochemistry

Biology

Colloidal gold

Biophysics

Nanoparticle

Inorganic chemistry

Chemistry

Materials science

Moiety

In vitro

Amyloid (mycology)

Biodistribution

Blood–brain barrier

Glutathione

Enantiomer

Biochemistry

Medicine

Pharmacology

Nature Communications

Preventing aggregation of amyloid beta (Aβ) peptides is a promising strategy for the treatment of Alzheimer’s disease (AD), and gold nanoparticles have previously been explored as a potential anti-Aβ therapeutics. Here we design and prepare 3.3 nm L- and D-glutathione stabilized gold nanoparticles (denoted as L3.3 and D3.3, respectively). Both chiral nanoparticles are able to inhibit aggregation of Aβ42 and cross the blood-brain barrier (BBB) following intravenous administration without noticeable toxicity. D3.3 possesses a larger binding affinity to Aβ42 and higher brain biodistribution compared with its enantiomer L3.3, giving rise to stronger inhibition of Aβ42 fibrillation and better rescue of behavioral impairments in AD model mice. This conjugation of a small nanoparticle with chiral recognition moiety provides a potential therapeutic approach for AD.

Chiral gold nanoparticles enantioselectively rescue memory deficits in a mouse model of Alzheimer’s disease