Lysosomal Cathepsin A Plays a Significant Role in the Processing of Endogenous Bioactive Peptides

Timur, Zehra Kevser; Demir, Secil Akyildiz; Seyrantepe, Volkan

doi:10.3389/fmolb.2016.00068

Cited by 34 publications

(27 citation statements)

References 29 publications

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“…Galactosialidosis #256540 CTSA Accumulation of sialylated oligosaccharides and glycoproteins in lysosomes due to complete deficiency in neuraminidase-1 and partial deficiency in beta-galactosidase. [13,43,119,121,122] Neuronal ceroid lipofuscinosis 10 #610127 CTSD Impaired lysosomal degradation and aberrant autophagy. [42,43,130,131] Neuronal ceroid lipofuscinosis 13 #615362 CTSF Impaired lysosomal degradation and aberrant autophagy.…”

Section: Gene Deficiency Biological Effect Referencesmentioning

confidence: 99%

“…Defects in CTSA expression and/or activity result in a complete or partial deficiency of NEU-1 and β-GAL enzyme activities, leading to the accumulation of sialylated oligosaccharides and glycoproteins in lysosomes, and excretion of the formers in body fluids. Moreover, CTSA participates in processing vasoactive peptides and the formation of elastic fibers [119].…”

Section: Gene Deficiency Biological Effect Referencesmentioning

confidence: 99%

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Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Pasquale

Moles

Pavone

2020

Cells

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Cathepsins (CTSs) are ubiquitously expressed proteases normally found in the endolysosomal compartment where they mediate protein degradation and turnover. However, CTSs are also found in the cytoplasm, nucleus, and extracellular matrix where they actively participate in cell signaling, protein processing, and trafficking through the plasma and nuclear membranes and between intracellular organelles. Dysregulation in CTS expression and/or activity disrupts cellular homeostasis, thus contributing to many human diseases, including inflammatory and cardiovascular diseases, neurodegenerative disorders, diabetes, obesity, cancer, kidney dysfunction, and others. This review aimed to highlight the involvement of CTSs in inherited lysosomal storage disorders, with a primary focus to the emerging evidence on the role of CTSs in the pathophysiology of Mucopolysaccharidoses (MPSs). These latter diseases are characterized by severe neurological, skeletal and cardiovascular phenotypes, and no effective cure exists to date. The advance in the knowledge of the molecular mechanisms underlying the activity of CTSs in MPSs may open a new challenge for the development of novel therapeutic approaches for the cure of such intractable diseases.

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Section: Gene Deficiency Biological Effect Referencesmentioning

confidence: 99%

Section: Gene Deficiency Biological Effect Referencesmentioning

confidence: 99%

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Pasquale

Moles

Pavone

2020

Cells

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“…Cathepsin A causes the inactivation of bioactive peptides such as bradykinin, substance P, oxytocin, angiotensin I and endothelin-I. The role of this enzyme in galactosialidosis has come forth [16]. Cathepsin A can inhibit autophagy [5,6].…”

Section: Types Of Cathepsins and Their Functional Specificitiesmentioning

confidence: 99%

Cathepsins: Proteases that are vital for survival but can also be fatal

Patel

Homaei

El‐Seedi

et al. 2018

Biomedicine & Pharmacotherapy

172

108

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The state of enzymes in the human body determines the normal physiology or pathology, so all the six classes of enzymes are crucial. Proteases, the hydrolases, can be of several types based on the nucleophilic amino acid or the metal cofactor needed for their activity. Cathepsins are proteases with serine, cysteine, or aspartic acid residues as the nucleophiles, which are vital for digestion, coagulation, immune response, adipogenesis, hormone liberation, peptide synthesis, among a litany of other functions. But inflammatory state radically affects their normal roles. Released from the lysosomes, they degrade extracellular matrix proteins such as collagen and elastin, mediating parasite infection, autoimmune diseases, tumor metastasis, cardiovascular issues, and neural degeneration, among other health hazards. Over the years, the different types and isoforms of cathepsin, their optimal pH and functions have been studied, yet much information is still elusive. By taming and harnessing cathepsins, by inhibitors and judicious lifestyle, a gamut of malignancies can be resolved. This review discusses these aspects, which can be of clinical relevance.

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“…Some of these enzymes, on the other hand, can be stored inside cells, such as neutrophil serine proteases, that are localized in neutrophil granules and are secreted into the extracellular compartment upon reaction to specific stimuli . There are also some serine proteases, for example, cathepsin A or tripeptidyl‐peptidase I, that reside in the acidic environment of lysosomes . The most popular serine protease in terms of diagnostic applications is kallikrein 3, also known as prostate‐specific antigen (PSA).…”

Section: Proteases In Health and Diseasementioning

confidence: 99%

Protease‐activated prodrugs: strategies, challenges, and future directions

Poręba

2020

The FEBS Journal

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Proteases play critical roles in virtually all biological processes, including proliferation, cell death and survival, protein turnover, and migration. However, when dysregulated, these enzymes contribute to the progression of multiple diseases, with cancer, neurodegenerative disorders, inflammation, and blood disorders being the most prominent examples. For a long time, disease-associated proteases have been used for the activation of various prodrugs due to their well-characterized catalytic activity and ability to selectively cleave only those substrates that strictly correspond with their active site architecture. To date, versatile peptide sequences that are cleaved by proteases in a site-specific manner have been utilized as bioactive linkers for the targeted delivery of multiple types of cargo, including fluorescent dyes, photosensitizers, cytotoxic drugs, antibiotics, and pro-antibodies. This platform is highly adaptive, as multiple protease-labile conjugates have already been developed, some of which are currently in clinical use for cancer treatment. In this review, recent advancements in the development of novel protease-cleavable linkers for selective drug delivery are described. Moreover, the current limitations regarding the selectivity of linkers are Abbreviations AAC, antibody-antibiotic conjugate; Ab, antibody; ACC, 7-amino-4-carbamoylmethylcoumarin; ADAM, a disintegrin and metalloproteinase; ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; ADC, antibody-drug conjugate; aPSs, activatable photosensitizers; BHQ-3, black hole quencher 3; Boc, tert-butyloxycarbonyl group; BT20, a type of mammary gland carcinoma; Cas9, CRISPR-associated protein 9;

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Lysosomal Cathepsin A Plays a Significant Role in the Processing of Endogenous Bioactive Peptides

Cited by 34 publications

References 29 publications

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

Cathepsins: Proteases that are vital for survival but can also be fatal

Protease‐activated prodrugs: strategies, challenges, and future directions

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