Chemical Strategies to Modulate Amyloidogenesis Associated with Neurodegenerative Diseases

Amyloidogenic peptides and proteins, including amyloid-β, tau, and α-synuclein, are key pathological factors in neurodegenerative diseases. Their misfolding and self-assembly into toxic oligomers and fibrils disrupt cellular homeostasis and lead to neuronal dysfunction. To address these pathogenic processes, diverse chemical strategies have been developed employing nanomaterials, small organic molecules, and metal complexes. These reagents chemically modify amyloidogenic peptides and proteins, thereby altering their aggregation pathways, attenuating associated toxicity, and demonstrating in vivo efficacy. In this review, we outline and discuss the design principles and mechanistic bases of these chemical interventions, with some examples that demonstrate anti-amyloidogenic effects. Collectively, these advances underscore the power of chemistry to modulate amyloid aggregation and provide mechanistic insights that can guide the development of innovative therapeutic strategies for amyloid-driven neurodegeneration.