Hsp90 inhibition and modulation of the proteome: Therapeutical implications for idiopathic pulmonary fibrosis (ipf)

RML Colunga Biancatelli, P Solopov… - International Journal of …, 2020 - mdpi.com
RML Colunga Biancatelli, P Solopov, B Gregory, JD Catravas
International Journal of Molecular Sciences, 2020mdpi.com
Idiopathic Pulmonary fibrosis (IPF) is a catastrophic disease with poor outcomes and limited
pharmacological approaches. Heat shock protein 90 (HSP90) has been recently involved in
the wound-healing pathological response that leads to collagen deposition in patients with
IPF and its inhibition represents an exciting drug target against the development of
pulmonary fibrosis. Under physiological conditions, HSP90 guarantees proteostasis through
the refolding of damaged proteins and the degradation of irreversibly damaged ones …
Idiopathic Pulmonary fibrosis (IPF) is a catastrophic disease with poor outcomes and limited pharmacological approaches. Heat shock protein 90 (HSP90) has been recently involved in the wound-healing pathological response that leads to collagen deposition in patients with IPF and its inhibition represents an exciting drug target against the development of pulmonary fibrosis. Under physiological conditions, HSP90 guarantees proteostasis through the refolding of damaged proteins and the degradation of irreversibly damaged ones. Additionally, its inhibition, by specific HSP90 inhibitors (e.g., 17 AAG, 17 DAG, and AUY-922) has proven beneficial in different preclinical models of human disease. HSP90 inhibition modulates a complex subset of kinases and interferes with intracellular signaling pathways and proteome regulation. In this review, we evaluated the current evidence and rationale for the use of HSP90 inhibitors in the treatment of pulmonary fibrosis, discussed the intracellular pathways involved, described the limitations of the current understanding and provided insights for future research.
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