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Bortezomib: a proteasome inhibitor for the treatment of autoimmune diseases

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Abstract

Autoimmune diseases (ADs) are conditions in which the immune system cannot distinguish self from non-self and, as a result, tissue injury occurs primarily due to the action of various inflammatory mediators. Different immunosuppressive agents are used for the treatment of patients with ADs, but some clinical cases develop resistance to currently available therapies. The proteasome inhibitor bortezomib (BTZ) is an approved agent for first-line therapy of people with multiple myeloma. BTZ has been shown to improve the symptoms of different ADs in animal models and ameliorated symptoms in patients with systemic lupus erythematous, rheumatoid arthritis, myasthenia gravis, neuromyelitis optica spectrum disorder, Chronic inflammatory demyelinating polyneuropathy, and autoimmune hematologic diseases that were nonresponsive to conventional therapies. Proteasome inhibition provides a potent strategy for treating ADs. BTZ represents a proteasome inhibitor that can potentially be used to treat AD patients resistant to conventional therapies.

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Abbreviations

Ab:

Anti-body

AchR:

Acetylcholine receptors

AD:

Autoimmune disease

AH:

Acquired hemophilia

AIA:

Adjuvant-induced arthritis

AIHA:

Autoimmune hemolytic anemia

AMR:

Antibody mediated rejection

APC:

Antigen presenting cell

AZA:

Azathioprine

BAFF:

B cell-activating factor

BTZ:

Borttezomib

C1q:

Complement component 1q

CDK:

Cyclin dependent kinase

CHOP:

C/EBP homologous protein

CIA:

Colagen-induced arthritis

CIDP:

Chronic inflammatory demyelinating polyneuropathy

COX:

Cyclooxygenase

CTLA4:

Cytotoxic T-lymphocyte-associated protein 4

CYP:

Cyclophosphamide

DC:

Dendritic cells

dsDNA:

Double strand DNA

EOMG:

Early onset myasthenia gravis

ER:

Endoplasmic reticulem

ESS:

Experimental Sjogren's syndrome

FDA:

Food and drug administration

FLS:

Fibroblast-like synoviocytes

FLS:

Fibroblast-like synoviocytes

GC:

Glucocorticoids

IAP:

Inhibitor of apoptosis

IBD:

Inflammatory bowel disease

IDO1:

Indoleamine 2,3-dioxygenase 1

IFN-γ:

Interferon-gamma

IL:

Interleukin

IV:

Intra venus

IVIG:

Intravenous immunoglobulins

IҡB:

Inhibitor of ҡB

LFA:

Lymphocyte function-associated antigen-1

LLPC:

Long-lived plasma cell

LN:

Lupus-like nephritis

LRP4:

Low-density lipoprotein receptor-related protein

MCL:

Mantle cell lymphoma

MDC:

Myeloid dendritic cell

MG:

Myasthenia gravis

MM:

Multiple myeloma

MMF:

Mycophenolate mofetile

MMP3:

Matrix metalloproteinases

MQ:

Macrophage

MTX:

Metathroxate

MUSK:

Mussel specific kinase

NET:

Neutrophil extracellular trap

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NK:

Natural killer

NMOSD:

Neuromyelitis optica spectrum disorder

NOD:

None-obese diabetic

NOS:

Nitric oxide synthase

PC:

Plasma cell

PCNA:

Proliferating cell nuclear antigen

pDC:

Plasmacytoid dendritic cell

PE:

Plasma exchange

PN:

Peripheral nephropathy

RA:

Rheumatoid arthritis

ROS:

Reactive oxygen species

SC:

Subcutaneously

SG:

Sjogren's syndrome

SLE:

Systemic lupus erythematous

SLPC:

Short-lived plasma cell

SS:

Sodium sulfate

TID:

Type I diabetes

TLR:

Toll-like receptor

TNFα:

Tumor necrosis factor alpha

TTP:

Thrombotic thrombocytopenic purpura

U1RNP:

U1 ribounucleoprotein

UPS:

Ubiquitin proteasome system

VLA-4:

Very late antigen-4

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Authors and Affiliations

  1. Biotechnology Department, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran

    Naeemeh Khalesi

  2. Research Center of Oils and Fats, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Shahla Korani

  3. Nanotechnology Research Center, Buali (Avicenna) Research Center, Mashhad University of Medical Science, Mashhad, Iran

    Mitra Korani

  4. Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, 64108, USA

    Thomas P. Johnston

  5. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  6. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran

    Amirhossein Sahebkar

  7. School of Medcine, The University of Western Australia, Perth, Australia

    Amirhossein Sahebkar

  8. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

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  1. Naeemeh Khalesi
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  2. Shahla Korani
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  3. Mitra Korani
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  5. Amirhossein Sahebkar
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Correspondence to Amirhossein Sahebkar.

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Khalesi, N., Korani, S., Korani, M. et al. Bortezomib: a proteasome inhibitor for the treatment of autoimmune diseases. Inflammopharmacol 29, 1291–1306 (2021). https://doi.org/10.1007/s10787-021-00863-2

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