Insulin-degrading enzyme (IDE) is a ubiquitous zinc peptidase of the inverzincin family, which has been initially discovered as the enzyme responsible for insulin catabolism; therefore, its involvement in the onset of diabetes has been largely investigated. However, further studies on IDE unraveled its ability to degrade several other polypeptides, such as β-amyloid, amylin, and glucagon, envisaging the possible implication of IDE dys-regulation in the "aggregopathies" and, in particular, in neurodegenerative diseases. Over the last decade, a novel scenario on IDE biology has emerged, pointing out a multi-functional role of this enzyme in several basic cellular processes. In particular, latest advances indicate that IDE behaves as a heat shock protein and modulates the ubiquitin-proteasome system, suggesting a major implication in proteins turnover and cell homeostasis. In addition, recent observations have highlighted that the regulation of glucose metabolism by IDE is not merely based on its largely proposed role in the degradation of insulin in vivo. There is increasing evidence that improper IDE function, regulation, or trafficking might contribute to the etiology of metabolic diseases. In addition, the enzymatic activity of IDE is affected by metals levels, thus suggesting a role also in the metal homeostasis (metallostasis), which is thought to be tightly linked to the malfunction of the "quality control" machinery of the cell. Focusing on the physiological role of IDE, we will address a comprehensive vision of the very complex scenario in which IDE takes part, outlining its crucial role in interconnecting several relevant cellular processes.

Tundo, G.r., Sbardella, D., Ciaccio, C., Grasso, G., Gioia, M., Coletta, A., et al. (2017). Multiple functions of insulin-degrading enzyme: a metabolic crosslight?. CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 52(5), 554-582 [10.1080/10409238.2017.1337707].

Multiple functions of insulin-degrading enzyme: a metabolic crosslight?

Tundo G. R.;Sbardella D.;Ciaccio C.;Gioia M.;Di Pierro D.;Marini S.;Coletta M.
2017-01-01

Abstract

Insulin-degrading enzyme (IDE) is a ubiquitous zinc peptidase of the inverzincin family, which has been initially discovered as the enzyme responsible for insulin catabolism; therefore, its involvement in the onset of diabetes has been largely investigated. However, further studies on IDE unraveled its ability to degrade several other polypeptides, such as β-amyloid, amylin, and glucagon, envisaging the possible implication of IDE dys-regulation in the "aggregopathies" and, in particular, in neurodegenerative diseases. Over the last decade, a novel scenario on IDE biology has emerged, pointing out a multi-functional role of this enzyme in several basic cellular processes. In particular, latest advances indicate that IDE behaves as a heat shock protein and modulates the ubiquitin-proteasome system, suggesting a major implication in proteins turnover and cell homeostasis. In addition, recent observations have highlighted that the regulation of glucose metabolism by IDE is not merely based on its largely proposed role in the degradation of insulin in vivo. There is increasing evidence that improper IDE function, regulation, or trafficking might contribute to the etiology of metabolic diseases. In addition, the enzymatic activity of IDE is affected by metals levels, thus suggesting a role also in the metal homeostasis (metallostasis), which is thought to be tightly linked to the malfunction of the "quality control" machinery of the cell. Focusing on the physiological role of IDE, we will address a comprehensive vision of the very complex scenario in which IDE takes part, outlining its crucial role in interconnecting several relevant cellular processes.
2017
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
Alzheimer’s disease; cell homeostasis; heat shock proteins; insulin-degrading enzyme; oxidized proteins turnover; type 2 diabetes; ubiquitin proteasome system; Alzheimer Disease; Animals; Diabetes Mellitus, Type 2; Humans; Insulysin; Protein Aggregation, Pathological; Protein Conformation
Tundo, G.r., Sbardella, D., Ciaccio, C., Grasso, G., Gioia, M., Coletta, A., et al. (2017). Multiple functions of insulin-degrading enzyme: a metabolic crosslight?. CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 52(5), 554-582 [10.1080/10409238.2017.1337707].
Tundo, Gr; Sbardella, D; Ciaccio, C; Grasso, G; Gioia, M; Coletta, A; Polticelli, F; Di Pierro, D; Milardi, D; Van Endert, P; Marini, S; Coletta, M...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/215076
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