Details

Autor(en) / Beteiligte

• Anand, Bibin G.
• Wu, Qi
• Karthivashan, Govindarajan
• Shejale, Kiran P.
• Amidian, Sara
• Wille, Holger
• Kar, Satyabrata

Titel

Mimosine functionalized gold nanoparticles (Mimo-AuNPs) suppress β-amyloid aggregation and neuronal toxicity

Ist Teil von

• Bioactive materials, 2021-12, Vol.6 (12), p.4491-4505

Ort / Verlag

Elsevier B.V

Erscheinungsjahr

2021

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Evidence suggests that increased level/aggregation of beta-amyloid (Aβ) peptides initiate neurodegeneration and subsequent development of Alzheimer's disease (AD). At present, there is no effective treatment for AD. In this study, we reported the effects of gold nanoparticles surface-functionalized with a plant-based amino acid mimosine (Mimo-AuNPs), which is found to cross the blood-brain barrier, on the Aβ fibrillization process and toxicity. Thioflavin T kinetic assays, fluorescence imaging and electron microscopy data showed that Mimo-AuNPs were able to suppress the spontaneous and seed-induced Aβ1-42 aggregation. Spectroscopic studies, molecular docking and biochemical analyses further revealed that Mimo-AuNPs stabilize Aβ1-42 to remain in its monomeric state by interacting with the hydrophobic domain of Aβ1-42 (i.e., Lys16 to Ala21) there by preventing a conformational shift towards the β-sheet structure. Additionally, Mimo-AuNPs were found to trigger the disassembly of matured Aβ1-42 fibers and increased neuronal viability by reducing phosphorylation of tau protein and the production of oxyradicals. Collectively, these results reveal that the surface-functionalization of gold nanoparticles with mimosine can attenuate Aβ fibrillization and neuronal toxicity. Thus, we propose Mimo-AuNPs may be used as a potential treatment strategy towards AD-related pathologies. [Display omitted] •Mimosine functionalized with gold nanoparticles (Mimo-AuNPs) can cross blood-brain barrier.•Mimo-AuNPs inhibit aggregation of Aβ peptides by interacting with its hydrophobic domain.•Mimo-AuNPs can trigger disassembly of pre-aggregated Aβ fibers.•Mimo-AuNPs can protect neurons against Aβ toxicity by attenuating intracellular signaling.