Polyoxometalates as Effective Nano-inhibitors of Amyloid Aggregation of Pro-inflammatory S100A9 Protein Involved in Neurodegenerative Diseases

Title	Polyoxometalates as Effective Nano-inhibitors of Amyloid Aggregation of Pro-inflammatory S100A9 Protein Involved in Neurodegenerative Diseases
Authors	Himanshu Chaudhary, Igor A. Iashchishyn, Nina V. Romanova, Mark A. Rambaran, Greta Musteikyte, Vytautas Smirnovas, Michael Holmboe, C. André Ohlin, Željko M. Svedružić, Ludmilla A. Morozova-Roche
Magazine	ACS Applied Materials & Interfaces
Date	06/03/2021
DOI	10.1021/acsami.1c04163
Introduction	The S100A9 protein, known for its pro-inflammatory and amyloidogenic properties, is a key player in the amyloid-neuroinflammatory cascade associated with neurodegenerative diseases. Polyoxometalates (POMs), a class of diverse nanomaterials, have shown potential in inhibiting amyloid formation. Our study highlights that two specific nanosized niobium POMs, Nb 10 and TiNb 9, significantly inhibit the assembly of S100A9 amyloid. Through ThT fluorescence kinetics analysis, we observed that both Nb 10 and TiNb 9 effectively reduce the rate and quantity of S100A9 amyloid formation. Atomic force microscopy confirmed the absence of elongated fibrils and only small aggregates in the presence of POMs. Molecular dynamics simulations demonstrated that these POMs interact with the S100A9 homo-dimer by forming ionic bonds with positively charged Lys-rich patches. Despite POM binding, the intrinsic Trp 88 environment remains unperturbed, and no significant changes in secondary or tertiary structures of S100A9 were observed. The local conformational changes at binding sites suggest a targeted interaction. Binding studies revealed a Kd of approximately 2.5 μM for POM interaction with S100A9. The region between Lys 50 and Lys 54, prone to amyloid formation, appears crucial for S100A9 self-assembly. These findings propose POMs as a therapeutic approach to target amyloid pathways in neurodegenerative diseases.
Quote	Himanshu Chaudhary, Igor A. Iashchishyn, Nina V. Romanova et al. Polyoxometalates as Effective Nano-inhibitors of Amyloid Aggregation of Pro-inflammatory S100A9 Protein Involved in Neurodegenerative Diseases. ACS Applied Materials & Interfaces. 2021. Vol. 13(23):26721-26734. DOI: 10.1021/acsami.1c04163
Element	Niobium (Nb) , Titanium (Ti)
Materials	Nanocomposites
Topics	Nanotechnology and Nanomaterials
Industry	Pharmaceutical Industry