TY - JOUR

T1 - The Mammalian Cysteine Protease Legumain in Health and Disease

AU - Solberg, Rigmor

AU - Lunde, Ngoc Nguyen

AU - Forbord, Karl Martin

AU - Okla, Meshail

AU - Kassem, Moustapha

AU - Jafari, Abbas

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022

Y1 - 2022

N2 - The cysteine protease legumain (also known as asparaginyl endopeptidase or δ-secretase) is the only known mammalian asparaginyl endopeptidase and is primarily localized to the endolysosomal system, although it is also found extracellularly as a secreted protein. Legumain is involved in the regulation of diverse biological processes and tissue homeostasis, and in the pathogenesis of various malignant and nonmalignant diseases. In addition to its proteolytic activity that leads to the degradation or activation of different substrates, legumain has also been shown to have a nonproteolytic ligase function. This review summarizes the current knowledge about legumain functions in health and disease, including kidney homeostasis, hematopoietic homeostasis, bone remodeling, cardiovascular and cerebrovascular diseases, fibrosis, aging and senescence, neurodegenerative diseases and cancer. In addition, this review addresses the effects of some marketed drugs on legumain. Expanding our knowledge on legumain will delineate the importance of this enzyme in regulating physiological processes and disease conditions.

AB - The cysteine protease legumain (also known as asparaginyl endopeptidase or δ-secretase) is the only known mammalian asparaginyl endopeptidase and is primarily localized to the endolysosomal system, although it is also found extracellularly as a secreted protein. Legumain is involved in the regulation of diverse biological processes and tissue homeostasis, and in the pathogenesis of various malignant and nonmalignant diseases. In addition to its proteolytic activity that leads to the degradation or activation of different substrates, legumain has also been shown to have a nonproteolytic ligase function. This review summarizes the current knowledge about legumain functions in health and disease, including kidney homeostasis, hematopoietic homeostasis, bone remodeling, cardiovascular and cerebrovascular diseases, fibrosis, aging and senescence, neurodegenerative diseases and cancer. In addition, this review addresses the effects of some marketed drugs on legumain. Expanding our knowledge on legumain will delineate the importance of this enzyme in regulating physiological processes and disease conditions.

KW - asaparginyl endopeptidae (AEP)

KW - asparaginyl carboksypeptidase (ACP)

KW - cysteine protease

KW - legumain

KW - peptide asparaginyl ligase (PAL)

KW - prolegumain

KW - δ-secretase

U2 - 10.3390/ijms232415983

DO - 10.3390/ijms232415983

M3 - Review

C2 - 36555634

AN - SCOPUS:85144730556

VL - 23

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 24

M1 - 15983

ER -