Effect of gold nanoparticles on the structure and neuroprotective function of protein L-isoaspartyl methyltransferase (PIMT)

Abstract

Fibrillation of peptides and proteins is implicated in various neurodegenerative diseases and is a global concern. Aging leads to the formation of abnormal isoaspartate (isoAsp) residues from isomerization of normal aspartates in proteins, triggering fibril formation that leads to neurodegenerative diseases. Protein L-isoaspartyl methyltransferase (PIMT) is a repair enzyme which recognizes and converts altered isoAsp residues back to normal aspartate. Here we report the effect of gold nanoparticles (AuNPs) of different sizes on the structure and function of PIMT. Spherical AuNPs, viz. AuNS5, AuNS50 and AuNS100 (the number indicating the diameter in nm) stabilize PIMT, with AuNS100 exhibiting the best efficacy, as evident from various biophysical experiments. Isothermal titration calorimetry (ITC) revealed endothermic, but entropy driven mode of binding of PIMT with all the three AuNSs. Methyltransferase activity assay showed enhanced activity of PIMT in presence of all AuNSs, the maximum being with AuNS100. The efficacy of PIMT in presence of AuNS100 was further demonstrated by the reduction of fibrillation of Aβ42, the peptide that is implicated in Alzheimer’s disease. The enhancement of anti-fibrillation activity of PIMT with AuNS100 was confirmed from cell survival assay with PC12 derived neuronal cells against Aβ42 induced neurotoxicity.

Protective mechanism of gold nanoparticles on human neural stem cells injured by β-amyloid protein through miR-21–5p/SOCS6 pathway

“…AuNPs are nanocarriers for intracellular drug or gene delivery. They have the characteristics of low toxicity, large speci c surface area, easy controllable surface assembly, and high speci city (Chatterjee et al 2021). Anand et al (Anand et al 2021) found that AuNPs surface-functionalized with a plant-based amino acid mimosine can attenuate Aβ brillization and neuronal toxicity.…”

The Role of Protein-L-isoaspartyl Methyltransferase (PIMT) in the Suppression of Toxicity of the Oligomeric Form of Aβ42, in Addition to the Inhibition of Its Fibrillization

“…The activity assay was carried out as described previously using a SAM-510 colorimetric assay kit (G-Bioscience, ), as previously described . The reaction was carried out in 0.1 M Tris–HCl buffer (pH 7.2) using monomeric Aβ42 as substrate for PIMT.…”

“…In this connection, it may be mentioned that the enzymatic activity and consequently the antifibrillar function of PIMT can be boosted by the addition of gold nanoparticles (AuNPs), which was demonstrated by administering PIMT-AuNP conjugates to Aβ42-induced PC12-derived neurons, showing a much higher cellular survival of the derived neurons compared to PIMT alone. 42 There is thus the possibility of enhancing the potential of PIMT against the toxicity induced by AβO oligomers also.…”

Antibiotic-Loaded Gold Nanoparticles: A Nano-Arsenal against ESBL Producer-Resistant Pathogens

“…Based on these above findings, the authors proposed that the bacterial pathogens received a sufficient quantity of β-lactam antibiotic that could saturate the ESBLs, and at the same time, antibiotic molecules that remain untouched by ESBLs might start their usual action on cell wall synthesis. In addition, AuNPs have the inherent ability to alter the structure and function of enzymes via interacting with them [ 94 , 95 , 96 , 97 , 98 ]; thus, it might be speculated that AuNPs could interact with ESBLs enzyme directly and disrupt their function.…”