HSP90 Inhibition and Modulation of the Proteome: Therapeutical Implications for Idiopathic Pulmonary Fibrosis (IPF)

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 repre...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-07, Vol.21 (15), p.5286
Main Authors: Colunga Biancatelli, Ruben Manuel Luciano, Solopov, Pavel, Gregory, Betsy, Catravas, John D
Format: Article
Language:English
Subjects:
Animals
Binding sites
Cell division
Collagen
Disease
Fibrosis
Heat shock proteins
HSP90 Heat-Shock Proteins - antagonists & inhibitors
HSP90 Heat-Shock Proteins - metabolism
Hsp90 protein
Humans
Hypoxia
Idiopathic Pulmonary Fibrosis - drug therapy
Idiopathic Pulmonary Fibrosis - metabolism
Idiopathic Pulmonary Fibrosis - pathology
Inflammation
Intracellular
Intracellular signalling
Kinases
Lavage
Lung diseases
Medical prognosis
Oxidative stress
Proteome - metabolism
Proteomes
Proteostasis
Pulmonary fibrosis
Review
Signal Transduction
Therapeutic targets
Transcription factors
Wound healing
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms21155286