Nanomaterial strategies for mitigating protein misfolding and neuroinflammation in neurodegenerative diseases

Abstract

Neurodegenerative disorders such as Alzheimer's disease are characterized by pathological protein misfolding, persistent neuroinflammation, and progressive synaptic deterioration. Nanoscale therapeutic platforms offer a versatile strategy for simultaneously suppressing pathogenic protein aggregation and modulating glial hyperactivation, thereby addressing the multifactorial nature of neurodegenerative pathology. Engineered AuNPs, carbon-based nanodots, and related constructs with negatively charged surfaces exhibit high affinity for amyloidogenic peptides, thereby limiting amyloid-β or tau fibrillization, while photothermal strategies using graphene or gold nanorods induce localized thermal disruption of preformed aggregates, enhancing their disassembly. In parallel, functionalized nanocarriers facilitate brain-targeted delivery of anti-inflammatory agents by leveraging receptor-mediated transcytosis or biomimetic cell membrane-camouflaging strategies, attenuating proinflammatory cytokines and promoting autophagic clearance. In vitro and in vivo models demonstrate integrated therapeutic benefits, including attenuation of plaque deposition, preservation of neuronal integrity, and recovery of cognitive performance. Despite remaining challenges in large-scale synthesis and long-term safety, evolving nanotechnologies offer a flexible and integrated platform capable of disrupting the pathogenic cycle linking protein misfolding, neuroinflammation, and disease progression.