HSP90 in Tissue-Migrating Nematodes: Therapeutic Potential and Implications for Parasite-Induced Pulmonary Injury

Tissue-migrating nematodes, including Toxocara spp., Ascaris spp., and Strongyloides spp., can cause substantial pulmonary injury during larval migration, characterized by inflammatory cell infiltration, disruption of the alveolar–capillary barrier, and increased vascular permeability. New therapeutic approaches should prioritize parasite control while also considering the recovery of injured pulmonary tissue. Heat shock protein 90 (HSP90), a highly conserved molecular chaperone involved in protein folding, stress adaptation, and cellular signaling, represents a potential therapeutic target in both parasitic nematodes and host tissues. Experimental studies have demonstrated that pharmacological inhibition of HSP90 reduces parasite viability and microfilarial output in selected filarial nematodes, supporting its potential as an anthelmintic strategy. Independently, HSP90 inhibitors have demonstrated protective effects against pulmonary endothelial dysfunction and experimental lung injury by preserving intercellular junctions, modulating inflammatory signaling pathways, and attenuating cytoskeletal rearrangement and vascular hyperpermeability. These findings suggest that HSP90 inhibition may offer a dual therapeutic approach by interfering with parasite survival while simultaneously limiting host pulmonary vascular and tissue injury. This review evaluates HSP90 inhibitors as potential anthelmintic agents against nematodes associated with pulmonary disease, particularly tissue-migrating larvae. Species- and stage-specific susceptibility, host toxicity, and preservation of protective immunity and tissue repair are discussed as key translational challenges.