basic FUNCTION
| involved in proteolytic degradation, cell invasion, and apoptosis |
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aspartic proteinase, bound to ceramide for proteolytic activity |
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cleaving procaspase 3, potentially recruited during apoptosis |
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involved in epidermal differentiation and major factor in the proteolysis of opsin |
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CTSD inhibitors block the formation of hyperphosphorylated tau fragments in hippocampus (lysosomal dysfunction) |
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play a key role in the homeostasis of neuronal structures |
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having a role in promoting cancer cell proliferation and invasion |
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playing an important role in intracellular cholesterol trafficking and ABCA1-mediated efflux |
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plays potentially an important role in the phagocytosis and lysosomal activation of macrophages/microglia during the central nervous system inflammation caused by trauma |
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predominant lysosomal protease, playing an important role in regulation of cellular apoptosis and mediating apoptosis induced by cytokines tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma |
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likely involved in beta-amyloidogenesis in Alzheimer disease (AD) |
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plays a significant role in the removal of AGE (advanced glycation end)-modified proteins |
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can likely function as an anti-apoptotic mediator by inducing autophagy under cellular stress |
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acts as an essential mediator to promote malignancy of benign prostatic epithelium |
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modulates the growth of fibroblasts by inhibiting LRP1 regulated intramembrane proteolysis (RIP) in the breast tumor microenvironment |
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acts as a transcriptional repressor, independently of its catalytic activity |
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acts as a nuclear transcriptional cofactor of TRPS1 to regulate ESR1+ breast cancer cells (BCC) proliferation and transformation in a non-proteolytic manner |
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CTSD enzymatic activity is a new factor affecting sensitivity of breast cancer cells to TNFSF10 |
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importance of CTSD for the maintenance of metabolism in central nervous system neurons, with neuronal cell death of CTSD-deficient Purkinje Cells distinct from apoptosis |
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CELLULAR PROCESS
| cell life, differentiation
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| cell life, cell death/apoptosis
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protein
| CST3 is a proteolytic target of cathepsin D (CTSD) and has a direct, causal impact on cell differentiation |
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CTSD is partly endocytosed by the LRP1 receptor and inhibits LRP1-regulated intramembrane proteolysis |
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MREG is likely required to maintain CTSD homeostasis in the RPE and likely plays a protective role in retinal health |
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critical regulatory role for that endogenous CTSD activity in dopaminergic cells in SNCA homeostasis which cannot be compensated for by increased CTSB |
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CTSD nuclear targeting is controlled by BAG6 |
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also binds to full-length TRPS1 |
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CTSD and NPC1 interaction with a new lysosomal function of NPC1 as a regulator of CTSD processing and activity |
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lysosomal enzyme cathepsin D (CTSD) mediates the proteolytic cleavage of PSAP precursor into saposins A-D |
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direct involvement of CLN3 in the regulation of CTSD activity |
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direct interaction between GRN and CTSD, and a combined reduction of GRN and CTSD synergistically reduced axonal outgrowth |
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cathepsin D is a protease that can activate VEGFC as well as VEGFD |
activated by
| by glycosaminoglycans (GAGs) |
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repressed by
| regulated by ESR1, which is crucial for long-distance regulation of CTSD expression involving a looping mechanism |
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corresponding disease(s)
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CLN10
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Other morbid association(s)
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Type | Gene Modification | Chromosome rearrangement | Protein expression | Protein Function
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constitutional
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| --low
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reduced by approximately 50p100 in monocyte-derived macrophages of low HDL-C subjects, most significantly those with cholesterol efflux defects but without mutations in ABCA1 | constitutional
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| --over
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significantly increased in the frontal cortex, in pyramidal and granule cells of the hippocampus, and in cerebellar neurons in autistic subjects as compared to controls | tumoral
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| --over
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in human breast carcinoma and many other tumor types | constitutional
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| loss of function
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partial loss of CTSD activity is sufficient to cause a reduction in lysosomal function, which in turn leads to SNCA aggregation and propagation of the aggregates | constitutional
| germinal mutation
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increased lysosomal storage due to CTSD deficiency causes oxidative damage in brain pericytes, subsequently resulting in an increased vessel diameter, enhanced permeability of the BBB and the infiltration of peripheral blood mononuclear cells (PBMCs) | constitutional
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| --low
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reduced CTSD level is an important factor that may contribute to the pathogenesis of preeclampsia, possibly by inhibiting normal trophoblastic invasion | |
Susceptibility
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almost a mild risk factor for sporadic Alzheimer disease (AD) |
Variant & Polymorphism
SNP
| (rs17571) of the cathepsin D gene associated with increased AD risk, in men but not in women |
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Candidate gene
Marker
| with eEF1s are promising markers for the detection of cellular senescence induced by a variety of treatments ( | |
| Therapy target
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System | Type | Disorder | Pubmed |
neurology | neurodegenerative | Parkinson/dementia Parkinsonism | |
upregulation of cathepsin D could be an additional therapeutic strategy to lessen alpha-synuclein burden in synucleinopathies | cancer | | | |
inhibition of autophagy could be a novel strategy for the adjuvant chemotherapy of CTSD-expressing cancers |
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| CtsD-deficient mice show severe visceral lesions like lymphopenia in addition to their central nervous system (CNS) phenotype of ceroid accumulation, microglia activation, and seizures | |
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