Lysosomal degradation. Medical search. Frequent questions

During autophagy, phagophores capture portions of cytoplasm and form double-membrane autophagosomes to deliver cargo for lysosomal degradation. (rupress.org)
Autophagy is a lysosomal degradation process that leads to the regeneration of new cells. (mendeley.com)
Autophagy is a well-conserved lysosomal degradation pathway that plays key roles in bacterial infections. (frontiersin.org)
Macroautophagy, hereafter referred to as autophagy, is a lysosomal degradative process that participates in cellular homeostasis by enabling the removal of defective organelles, protein aggregates, or intracellular microorganisms ( 1 ). (frontiersin.org)
The autophagy machinery targets intracellular pathogens for degradation, modulates inflammation, and participates in adaptive immune responses ( 3 - 5 ). (frontiersin.org)
Autophagy is an evolutionarily conserved cellular degradation pathway involving the digestion of intracellular components via the lysosomal pathway. (mdpi.com)
Autophagy is a conserved catabolic process that eliminates dysfunctional cytosolic biomolecules through vacuole-mediated sequestration and lysosomal degradation. (hindawi.com)
Autophagy is a cellular catabolic process that eliminates damaged cell organelles, unfolded proteins, and various intracellular pathogens through lysosomal degradation. (hindawi.com)
In general, autophagy degrades long-lived damaged intracellular proteins, in contrast to the ubiquitin-proteasome system, which controls the degradation of short-lived proteins [ 2 ]. (hindawi.com)
The therapeutic exploitation of intrinsic cellular functions including proteolysis pathways, autophagy and lysosomal degradation mechanisms will be explored. (slas.org)
Autophagy is a regulated lysosomal degradation which has the capacity to clear large protein/lipid complexes, toxic aggregates and cellular organelles. (michaeljfox.org)
Furthermore, autophagy-lysosomal function declines with age in human brain, which in part due to the high oxidative stress. (michaeljfox.org)
The loss of acidity would shut down or dampen lysosomal enzymes, causing autophagy to grind to a halt. (alzforum.org)
Macroautophagy (hereafter referred to as autophagy) is a vacuolar lysosomal degradation pathway for organelles and cytoplasmic macromolecules ( 9 ). (spandidos-publications.com)
2 Mitophagy is the selective degradation of mitochondria by autophagy. (moleculardevices.com)
Verapamil induces autophagy while chloroquine inhibits degradation of autophagosomes that lead to accumulation of particles. (moleculardevices.com)
Isoform-dependent lysosomal degradation and internalization of apolipoprotein E requires autophagy proteins. (bvsalud.org)

A possible role for the ubiquitin-proteasome pathway in the degradation of the receptor and ligand is discussed. (portlandpress.com)
Ubiquitin ligase Nedd4 promotes alpha-synuclein degradation by the endosomal-lysosomal pathway. (ox.ac.uk)
Here we show that the ubiquitin ligase Nedd4, which functions in the endosomal-lysosomal pathway, robustly ubiquitinates α-synuclein, unlike ligases previously implicated in its degradation. (ox.ac.uk)
Thus, ubiquitination by Nedd4 targets α-synuclein to the endosomal-lysosomal pathway and, by reducing α-synuclein content, may help protect against the pathogenesis of Parkinson disease and other α-synucleinopathies. (ox.ac.uk)
This corroborates the central role of the autophagosomal/lysosomal pathway in APP metabolism and shows that TSPAN6 is a crucial player in APP-CTF turnover. (url.edu)

Chloroquine treatment enhanced markers of both macroautophagy and apoptosis in MEFs but ultimately impaired lysosomal protein degradation. (jci.org)
The track will focus on emerging targets and mechanisms including protein degradation, non-coding RNAs and stabilising PPIs. (slas.org)
1) disruption of mitochondrial function leading to oxidative stress, (2) abnormalities in vesicle processing, (3) altered proteasomal and lysosomal protein degradation, and (4) a-synuclein aggregation The mutual neurotoxic processes provoked by mutations in these genes in concert with the biological disturbances produced by Mn, most likely, act in synchrony to contribute to the severity, characteristics and onset of both disorders. (cdc.gov)

Experiments with antibodies against different receptor tail sections show that degradation of the GHR cytosolic domain precedes degradation of the extracellular GH-binding domain. (portlandpress.com)
(A) xenophagy: selective capture and lysosomal degradation of cytosolic and vacuolar pathogens. (frontiersin.org)

Lysosomal function is critical for organismal homeostasis-mutations in genes encoding lysosomal proteins cause severe human disorders known as lysosomal storage diseases, and lysosome dysfunction is implicated in age-associated diseases including cancer, neurodegeneration and metabolic syndrome. (stanford.edu)

These findings specifically demonstrate that intermittent chloroquine use effectively prevents cancer in mouse models of 2 genetically distinct human cancer syndromes, Burkitt lymphoma and ataxia telangiectasia, suggesting that agents targeting lysosome-mediated degradation may be effective in cancer prevention. (jci.org)
The stepwise attachment of ubiquitin to the substrate receptor tyrosine kinase can lead to its removal from the plasma membrane and subsequent trafficking to the lysosome for degradation. (wikipedia.org)
1 The autophagosome vesicle then fuses with the lysosome to deliver its contents for degradation by lysosomal hydrolases. (moleculardevices.com)
More recently, the concept of lysosomal storage disease has been expanded to include deficiencies or defects in proteins necessary for the normal post-translational modification of lysosomal enzymes (which themselves are often glycoproteins), activator proteins, or proteins important for proper intracellular trafficking between the lysosome and other intracellular compartments. (medscape.com)

Thus chloroquine induces lysosomal stress and provokes a p53-dependent cell death that does not require caspase-mediated apoptosis. (jci.org)
Here, we found that PAR1 activation induces lysosomal degradation of Src. (tmu.edu.tw)

After the degradation of damaged proteins and lipids, amino acids and fatty acids are released into the cytoplasm and recycled for new biosynthesis of cellular components or energy production [ 4 ]. (hindawi.com)
Emerging evidence suggests that multiple levels of mitochondrial surveillance are required, ranging from focal removal of damaged proteins and lipids to full degradation of dysfunctional organelles. (duke.edu)

2019. Human cytomegalovirus interactome analysis identifies degradation hubs, domain associations and viral protein functions . (cardiff.ac.uk)

GH internalization and degradation are inhibited when cells are treated with proteasome inhibitors. (portlandpress.com)
However, Src activity is neither required for agonist-induced PAR1 internalization nor required for Src degradation upon PAR1 activation. (tmu.edu.tw)

Classically, lysosomal storage diseases encompassed only enzyme deficiencies of the lysosomal hydrolases. (medscape.com)

Krabbe disease, also known as globoid cell leukodystrophy or galactosylceramide lipidosis, is an autosomal-recessive sphingolipidosis caused by deficient activity of the lysosomal hydrolase galactosylceramide beta-galactosidase (GALC). (medscape.com)
It also plays a role in the LYSOSOMES by protecting BETA-GALACTOSIDASE and NEURAMINIDASE from degradation. (bvsalud.org)

Conclusions: TSPAN6 is a key player in the bifurcation between lysosomal-dependent degradation and exosome mediated secretion of APP-CTF. (url.edu)

Lysosomal enzymes then degrade the cargo contained within the autolysosome. (hindawi.com)

Lysosomal degradation of depolarized mitochondria is rate-limiting in OPTN-dependent neuronal mitophagy. (duke.edu)
Lysosomal storage diseases are generally classified by the accumulated substrate and include the sphingolipidoses, oligosaccharidoses, mucolipidoses, mucopolysaccharidoses (MPSs), lipoprotein storage disorders, lysosomal transport defects, neuronal ceroid lipofuscinoses and others. (medscape.com)

One of the most studied is probably xenophagy, the selective capture and degradation of intracellular bacteria by lysosomes. (frontiersin.org)
The selective degradation of sirtuins via macroautophagy in the MPP + model of Parkinson's disease is promoted by conserved oxidation sites. (unimedizin-mainz.de)

In human cells, Nedd4 overexpression enhances α-synuclein ubiquitination and clearance by a lysosomal process requiring components of the endosomal-sorting complex required for transport. (ox.ac.uk)
Ubiquitination is the process of chemically attaching ubiquitin monomers to a protein, thereby targeting it for degradation. (wikipedia.org)
Hypertonicity-responsive ubiquitin ligase RNF183 promotes Na, K-ATPase lysosomal degradation through ubiquitination of its β1 subunit. (nih.gov)

This has led to active clinical trials evaluating the safety and efficacy of intrathecal enzyme delivery in several lysosomal storage diseases (see www.ClinicalTrials.gov ). (medscape.com)

Age of onset and clinical manifestations may vary widely among patients with a given lysosomal storage disease, and significant phenotypic heterogeneity between family members carrying identical mutations has been reported. (medscape.com)

show that mitochondria can be expelled from cells via extracellular vesicles as a route of quality control that is an alternative to lysosomal degradation. (nature.com)
Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons. (duke.edu)

Lysosomal inhibitors prolong the half-life of both receptor and ligand. (portlandpress.com)
Salinomycin co-treatment enhances tamoxifen cytotoxicity in luminal A breast tumor cells by facilitating lysosomal degradation of receptor tyrosine kinases. (mpg.de)

We apply this knowledge to understand how lysosomal dysfunction leads to human diseases including neurodegeneration, cancer and metabolic syndrome. (stanford.edu)
Lysosomal storage diseases describe a heterogeneous group of dozens of rare inherited disorders characterized by the accumulation of undigested or partially digested macromolecules, which ultimately results in cellular dysfunction and clinical abnormalities. (medscape.com)

Gene therapy is experimental but in the future may help correct both somatic and neurologic abnormalities in a lysosomal storage disorder. (medscape.com)

In general, transplantation yields the best results when performed early in the course of the disease (ie, in an asymptomatic affected sibling of a child with a lysosomal storage disorder), in centers with experience in performing transplantations to treat inherited metabolic disorders, and in patients healthy enough to tolerate the conditioning and transplantation regimen. (medscape.com)

H37Rv-infected murine bone marrow-derived macrophages (BMDMs) displayed both lysosomal leakage, with release of CTSB into the cytosol, as well as increased levels of mature IL-1β. (frontiersin.org)
These observations suggest that during Mtb infection, lysosomal release of activated CTSB and possibly other cathepsins inhibitable by CA07-Me is critical for the induction of inflammasome-mediated IL-1β processing by regulating NLRP3-inflammasome assembly in the cytosol. (frontiersin.org)
The fully functional autolysosome then degrades the autolysosomal cargo and releases the degradation products into the cytosol for recycling. (hindawi.com)

Glycosylasparaginase is essential for the degradation of Asn-linked glycoproteins. (ebi.ac.uk)

Here we show that a GHR truncated at residue 369 can enter the cells in the presence of a proteasome inhibitor, but that the subsequent lysosomal degradation of GH is blocked. (portlandpress.com)

Recent progress in lysosomal alpha-mannosidase and its deficiency. (medlineplus.gov)

These vesicles seemed to fuse normally with lysosomes in the lipid-rich cells, but the degradation process stalled. (alzforum.org)
Relying upon a delicate balance between matrix synthesis and degradation, the extracellular matrix (ECM), including collagen and proteoglycans, undergoes a process of remodeling in normal IVDs. (spandidos-publications.com)

Src is associated and trafficked together with activated PAR1 to early endosomes and then sorted to lysosomes for degradation. (tmu.edu.tw)

More than 50 lysosomal storage diseases have been described, some of which are discussed in this article. (medscape.com)
Thus far, ERT has been largely unsuccessful in improving central nervous system manifestations of the lysosomal storage diseases, putatively due to difficulty in penetrating the blood-brain barrier. (medscape.com)
Accumulated data indicate that hematopoietic stem cell transplantation may be effective under optimal conditions in preventing the progression of central nervous system symptoms in neuronopathic forms of lysosomal storage diseases, including some of the mucopolysaccharidoses, oligosaccharidoses, sphingolipidoses, and lipidoses. (medscape.com)
The availability of both ERT and hematopoietic stem cell transplantation has prompted ongoing consideration of newborn screening efforts to diagnose lysosomal storage diseases. (medscape.com)

We show that PAR1 activation triggers endocytosis-dependent lysosomal degradation of Src in both human embryonic kidney 293 and human umbilical vein endothelial cells. (tmu.edu.tw)
It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. (nih.gov)

Intracellular transport of human lysosomal alpha-mannosidase and alpha-mannosidosis-related mutants. (medlineplus.gov)

Lysosomal cathepsin B (CTSB) has been proposed to play a role in the induction of acute inflammation. (frontiersin.org)

This latter step is mediated by a second Beclin-1 complex, lysosomal-associated membrane protein 1 (LAMP1), and a fusion machinery including SNARE syntaxin-17. (frontiersin.org)

TSPAN6 affects autophagosome-lysosomal fusion slowing down the degradation of APP-CTF. (url.edu)

Muscle development and regeneration controlled by AUF1-mediated stage-specific degradation of fate-determining checkpoint mRNAs. (sfu.ca)

Blocking agonist-induced endocytosis of PAR1 by inhibition of dynamin activity suppresses PAR1-induced degradation of Src. (tmu.edu.tw)

Anatomy30

Organisms16

Diseases1

Chemicals and Drugs126

Analytical, Diagnostic and Therapeutic Techniques and Equipment25

Phenomena and Processes53

Disciplines and Occupations2

Technology, Industry, Agriculture2

Information Science3

Health Care3

Autophagy17

Pathway5

Protein degradation3

Cytosolic2

Known as lysosomal1

Lysosome4

Induces2

Proteins and lipids2

20191

Internalization2

Hydrolases1

Beta-galactosidase2

Exosome1

Enzymes1

Neuronal2

Selective2

Ubiquitination3

Enzyme1

Mutations1

Mitochondria2

Receptor2

Dysfunction2

Abnormalities1

Disorders1

Cytosol3

Glycoproteins1

Subsequent1

Deficiency1

Process2

Endosomes1

Storage4

Kidney2

Human1

Role1

Complex1

Fusion1

Development1

Activity1