Sulfonamide Inhibitors of Amyloid Aggregation: A Promising Path against Neurodegenerative Diseases

Sulfonamides, a versatile class of compounds, show promise in inhibiting protein amyloid aggregation, a key process in diseases like Alzheimer's and Parkinson's. Studies reveal that sulfonamide derivatives can reduce fibril formation and stabilize non-aggregated proteins, offering potential as multitarget therapeutic agents. Further research is needed to optimize their clinical applications and explore their mechanisms of action.

Protein amyloid aggregation is a critical pathological process implicated in nearly 50 amyloid-related diseases, including Alzheimer's and Parkinson's diseases. This review highlights the potential of sulfonamides, a versatile class of compounds recognized for their diverse pharmacological properties, as modulators of protein aggregation. We provide an overview of studies examining the efficacy of sulfonamide derivatives in inhibiting the aggregation of various amyloidogenic proteins, including amyloid-beta, tau, alpha-synuclein, insulin, and transthyretin. In vitro assays, such as Thioflavin T fluorescence and high-resolution imaging techniques, have shown that certain sulfonamides can significantly inhibit fibril formation and promote the stabilization of non-aggregated protein states. The potential for sulfonamides to serve as multi-target agents offers new avenues for therapeutic development. By integrating findings from current research, we support a proposal that sulfonamide-based compounds could play a pivotal role in addressing the multifaceted nature of amyloid-related neurodegenerative diseases, paving the way for innovative therapeutic strategies.