Immunoproteasome in cancer and neuropathologies: A new therapeutic target?

Elena Bellavista, Federico Andreoli, Marco Daniele Parenti, Morena Martucci, Aurelia Santoro, Stefano Salvioli, Miriam Capri, Agostino Baruzzi, Alberto Del Rio, Claudio Franceschi, Michele Mishto

Research output: Contribution to journalArticle

Abstract

Immunoproteasome is an emerging biological target that constitutes a key element not only in antigen presentation but also in T cell and cytokine regulation as well as cellular homeostasis. Respect to standard proteasome, the inducible expression and different sensitivity towards activity modulators of immunoproteasome render it a potential therapeutic target for tumours and central nervous system diseases. In this review we report the cutting edge studies for understanding when immunoproteasome expression is induced and how it regulates pivotal pathways involved in tumours and neuropathologies, including apoptosis and inflammation. We emphasize its role as a new pharmacological target by describing the recent medicinal chemistry efforts aimed at design selective small-molecule modulators of both standard- and immuno-proteasome forms. Finally, we also present an in silico model of the human immunoproteasome structure by the major molecular differences with the 20S standard proteasome and discuss the perspective for the design of novel specific smallmolecule modulators for the different proteasome isoforms.

Original languageEnglish
Pages (from-to)702-718
Number of pages17
JournalCurrent Pharmaceutical Design
Volume19
Issue number4
Publication statusPublished - 2013

Fingerprint

Proteasome Endopeptidase Complex
Neoplasms
Pharmaceutical Chemistry
Central Nervous System Diseases
Antigen Presentation
Therapeutics
Molecular Structure
Computer Simulation
Protein Isoforms
Homeostasis
Pharmacology
Apoptosis
Cytokines
Inflammation
T-Lymphocytes
Neuropathology

Keywords

  • Alzheimer's disease
  • Brain
  • Cancer
  • Computer-aided drug design
  • Epilepsy
  • Immunoproteasome
  • Immunoproteasome model
  • Multiple sclerosis
  • Proteasome enhancers
  • Selective inhibitor
  • Standard proteasome
  • Tumour

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

Bellavista, E., Andreoli, F., Parenti, M. D., Martucci, M., Santoro, A., Salvioli, S., ... Mishto, M. (2013). Immunoproteasome in cancer and neuropathologies: A new therapeutic target? Current Pharmaceutical Design, 19(4), 702-718.

Immunoproteasome in cancer and neuropathologies : A new therapeutic target? / Bellavista, Elena; Andreoli, Federico; Parenti, Marco Daniele; Martucci, Morena; Santoro, Aurelia; Salvioli, Stefano; Capri, Miriam; Baruzzi, Agostino; Del Rio, Alberto; Franceschi, Claudio; Mishto, Michele.

In: Current Pharmaceutical Design, Vol. 19, No. 4, 2013, p. 702-718.

Research output: Contribution to journalArticle

Bellavista, E, Andreoli, F, Parenti, MD, Martucci, M, Santoro, A, Salvioli, S, Capri, M, Baruzzi, A, Del Rio, A, Franceschi, C & Mishto, M 2013, 'Immunoproteasome in cancer and neuropathologies: A new therapeutic target?', Current Pharmaceutical Design, vol. 19, no. 4, pp. 702-718.
Bellavista E, Andreoli F, Parenti MD, Martucci M, Santoro A, Salvioli S et al. Immunoproteasome in cancer and neuropathologies: A new therapeutic target? Current Pharmaceutical Design. 2013;19(4):702-718.
Bellavista, Elena ; Andreoli, Federico ; Parenti, Marco Daniele ; Martucci, Morena ; Santoro, Aurelia ; Salvioli, Stefano ; Capri, Miriam ; Baruzzi, Agostino ; Del Rio, Alberto ; Franceschi, Claudio ; Mishto, Michele. / Immunoproteasome in cancer and neuropathologies : A new therapeutic target?. In: Current Pharmaceutical Design. 2013 ; Vol. 19, No. 4. pp. 702-718.
@article{25e4162e53e94679aa30fac050228435,
title = "Immunoproteasome in cancer and neuropathologies: A new therapeutic target?",
abstract = "Immunoproteasome is an emerging biological target that constitutes a key element not only in antigen presentation but also in T cell and cytokine regulation as well as cellular homeostasis. Respect to standard proteasome, the inducible expression and different sensitivity towards activity modulators of immunoproteasome render it a potential therapeutic target for tumours and central nervous system diseases. In this review we report the cutting edge studies for understanding when immunoproteasome expression is induced and how it regulates pivotal pathways involved in tumours and neuropathologies, including apoptosis and inflammation. We emphasize its role as a new pharmacological target by describing the recent medicinal chemistry efforts aimed at design selective small-molecule modulators of both standard- and immuno-proteasome forms. Finally, we also present an in silico model of the human immunoproteasome structure by the major molecular differences with the 20S standard proteasome and discuss the perspective for the design of novel specific smallmolecule modulators for the different proteasome isoforms.",
keywords = "Alzheimer's disease, Brain, Cancer, Computer-aided drug design, Epilepsy, Immunoproteasome, Immunoproteasome model, Multiple sclerosis, Proteasome enhancers, Selective inhibitor, Standard proteasome, Tumour",
author = "Elena Bellavista and Federico Andreoli and Parenti, {Marco Daniele} and Morena Martucci and Aurelia Santoro and Stefano Salvioli and Miriam Capri and Agostino Baruzzi and {Del Rio}, Alberto and Claudio Franceschi and Michele Mishto",
year = "2013",
language = "English",
volume = "19",
pages = "702--718",
journal = "Current Pharmaceutical Design",
issn = "1381-6128",
publisher = "Bentham Science Publishers B.V.",
number = "4",

}

TY - JOUR

T1 - Immunoproteasome in cancer and neuropathologies

T2 - A new therapeutic target?

AU - Bellavista, Elena

AU - Andreoli, Federico

AU - Parenti, Marco Daniele

AU - Martucci, Morena

AU - Santoro, Aurelia

AU - Salvioli, Stefano

AU - Capri, Miriam

AU - Baruzzi, Agostino

AU - Del Rio, Alberto

AU - Franceschi, Claudio

AU - Mishto, Michele

PY - 2013

Y1 - 2013

N2 - Immunoproteasome is an emerging biological target that constitutes a key element not only in antigen presentation but also in T cell and cytokine regulation as well as cellular homeostasis. Respect to standard proteasome, the inducible expression and different sensitivity towards activity modulators of immunoproteasome render it a potential therapeutic target for tumours and central nervous system diseases. In this review we report the cutting edge studies for understanding when immunoproteasome expression is induced and how it regulates pivotal pathways involved in tumours and neuropathologies, including apoptosis and inflammation. We emphasize its role as a new pharmacological target by describing the recent medicinal chemistry efforts aimed at design selective small-molecule modulators of both standard- and immuno-proteasome forms. Finally, we also present an in silico model of the human immunoproteasome structure by the major molecular differences with the 20S standard proteasome and discuss the perspective for the design of novel specific smallmolecule modulators for the different proteasome isoforms.

AB - Immunoproteasome is an emerging biological target that constitutes a key element not only in antigen presentation but also in T cell and cytokine regulation as well as cellular homeostasis. Respect to standard proteasome, the inducible expression and different sensitivity towards activity modulators of immunoproteasome render it a potential therapeutic target for tumours and central nervous system diseases. In this review we report the cutting edge studies for understanding when immunoproteasome expression is induced and how it regulates pivotal pathways involved in tumours and neuropathologies, including apoptosis and inflammation. We emphasize its role as a new pharmacological target by describing the recent medicinal chemistry efforts aimed at design selective small-molecule modulators of both standard- and immuno-proteasome forms. Finally, we also present an in silico model of the human immunoproteasome structure by the major molecular differences with the 20S standard proteasome and discuss the perspective for the design of novel specific smallmolecule modulators for the different proteasome isoforms.

KW - Alzheimer's disease

KW - Brain

KW - Cancer

KW - Computer-aided drug design

KW - Epilepsy

KW - Immunoproteasome

KW - Immunoproteasome model

KW - Multiple sclerosis

KW - Proteasome enhancers

KW - Selective inhibitor

KW - Standard proteasome

KW - Tumour

UR - http://www.scopus.com/inward/record.url?scp=84876702879&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876702879&partnerID=8YFLogxK

M3 - Article

C2 - 23016859

AN - SCOPUS:84876702879

VL - 19

SP - 702

EP - 718

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

IS - 4

ER -