The transport of soluble lysosomal hydrolases from the Golgi complex to lysosomes

Castino, Roberta; Isidoro, Ciro

doi:10.1007/978-3-211-76310-0_25

Cited by 2 publications

(3 citation statements)

References 69 publications

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“…In mouse embryonic fibroblasts cathepsin B and D are known to be captured by the membrane proteins LRP1 (low-density lipoprotein receptor-related protein 1) and LDLR (low-density lipoprotein receptor) [ 41 , 42 ]. While procathepsin D is known to complex with sphingolipid activator precursor protein prosaposin, procathepsin B is known to rely on its membrane association to enter lysosomes independent of M6P route [ 43 , 44 , 45 ]. Recently, type 1 transmembrane protein SEZ6L2 was linked with sorting of cathepsin D in neurons [ 46 ].…”

Section: Cathepsins In Lysosomesmentioning

confidence: 99%

The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

Yadati

Houben

Bitorina

et al. 2020

Cells

322

198

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Cathepsins are the most abundant lysosomal proteases that are mainly found in acidic endo/lysosomal compartments where they play a vital role in intracellular protein degradation, energy metabolism, and immune responses among a host of other functions. The discovery that cathepsins are secreted and remain functionally active outside of the lysosome has caused a paradigm shift. Contemporary research has unraveled many versatile functions of cathepsins in extralysosomal locations including cytosol and extracellular space. Nevertheless, extracellular cathepsins are majorly upregulated in pathological states and are implicated in a wide range of diseases including cancer and cardiovascular diseases. Taking advantage of the differential expression of the cathepsins during pathological conditions, much research is focused on using cathepsins as diagnostic markers and therapeutic targets. A tailored therapeutic approach using selective cathepsin inhibitors is constantly emerging to be safe and efficient. Moreover, recent development of proteomic-based approaches for the identification of novel physiological substrates offers a major opportunity to understand the mechanism of cathepsin action. In this review, we summarize the available evidence regarding the role of cathepsins in health and disease, discuss their potential as biomarkers of disease progression, and shed light on the potential of extracellular cathepsin inhibitors as safe therapeutic tools.

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Section: Cathepsins In Lysosomesmentioning

confidence: 99%

The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

Yadati

Houben

Bitorina

et al. 2020

Cells

322

198

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“…B). The transport of pro‐cathepsin D from the Golgi complex to the downstream acidic compartments, namely, the early and late endosomes, may engage different pathways, involving the interaction with specific receptors or the trafficking as a passenger‐bystander . However, the most relevant pathway for the targeting of pro‐cathepsin D into the endosomal compartment relies on two receptors specific for the mannose‐6‐phosphate (M6P) group, a tag that marks the majority of lysosome‐directed soluble enzymes .…”

Section: Introductionmentioning

confidence: 99%

“…The product of this gene interacts with and stabilizes sortilin. The latter, also known as neurotensin receptor 3, is a neuronal membrane receptor for neuromediators and growth factors and is also involved in the Golgi‐to‐lysosome transport of the pro‐saposin‐pro‐cathepsin D complex . Mamo et al .…”

Section: Introductionmentioning

confidence: 99%

The Role of Cathepsin D in the Pathogenesis of Human Neurodegenerative Disorders

Vidoni

Follo

Savino

et al. 2016

Medicinal Research Reviews

Self Cite

127

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In familial neurodegenerative disorders, protein aggregates form continuously because of genetic mutations that drive the synthesis of truncated or unfolded proteins. The oxidative stress imposed by neurotransmitters and environmental neurotoxins constitutes an additional threat to the folding of the proteins and the integrity of organelle membranes in neurons. Failure in degrading such altered materials compromises the function of neurons and eventually leads to neurodegeneration. The lysosomal proteolytic enzyme Cathepsin D is the only aspartic-type protease ubiquitously expressed in all the cells of the human body, and it is expressed at high level in the brain. In general, cathepsin D mediated proteolysis is essential to neuronal cell homeostasis through the degradation of unfolded or oxidized protein aggregates delivered to lysosomes via autophagy or endocytosis. More specifically, many altered neuronal proteins that hallmark neurodegenerative diseases (e.g., the amyloid precursor, α-synuclein, and huntingtin) are physiologic substrates of cathepsin D and would abnormally accumulate if not efficiently degraded by this enzyme. Furthermore, experimental evidence indicates that cathepsin D activity is linked to the metabolism of cholesterol and of glycosaminoglycans, which accounts for its involvement in neuronal plasticity. This review focuses on the unique role of cathepsin D mediated proteolysis in the pathogenesis of human neurodegenerative diseases.

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The transport of soluble lysosomal hydrolases from the Golgi complex to lysosomes

Cited by 2 publications

References 69 publications

The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management

The Role of Cathepsin D in the Pathogenesis of Human Neurodegenerative Disorders

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