Identification of Cathepsin D as a Plasma Biomarker for Alzheimer’s Disease

Kim, Jae-Whan; Jung, Soonyoung; Kim, Youngbin; Heo, Hansol; Hong, Chang-Hyung; Seo, Soonbeom; Choi, Si‐Sun; Son, Sangjoon; Lee, Seongju; Chang, Jaerak

doi:10.3390/cells10010138

Cited by 22 publications

(14 citation statements)

References 59 publications

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“…LMNA (lamin A/C) [187], PFKFB3 [188], TRAF2 [189], ADORA2B [190], ACADS (acyl-CoA dehydrogenase short chain) [191], IRF7 [192], ASL (argininosuccinatelyase) [193], IL15 [194], PIK3R1 [195], OSM (oncostatin M) [196], SOCS3 [197], CHD9 [198], IFI44L [199], GNLY (granulysin) [200], FLNB (filamin B) [201], IL1R1 [202], SETD3 [203], TP53 [204], BRD4 [205], COX2 [206], HSP90AB1 [207], SLC7A1 [208], ND2 [209] and COX1 [210] have been reported to be associated with hypertension. LMNA (lamin A/C) [211], INPP5K [212], SCYL1 [213], AKR7A2 [214], TRAF2 [215], SLC11A2 [216], NEU1 [217], SNAP29 [218], DUSP22 [219], P2RX4 [220], ADORA2B [221], NAXD (NAD(P)HX dehydratase) [222], FEZ1 [223], TBK1 [224], GRN (granulin precursor) [225], ATG4D [226], CTSD (cathepsin D) [227], PPP2R5D [228], IRF7 [229], ACAA1 [230], S1PR1 [231], PGRMC1 [169], MAPK14 [232], IL15 [233], OSM (oncostatin M) [234], GBA (glucosylceramidase beta) [235], SOCS3 [236], GLUL (glutamate-ammonia ligase) [175], MON1A [237], LMAN2L [238], RHOC (ras homolog family member C) [239], TUBB2A [240], CHP1 [241], TP53 [242], ATXN1 [243], JARID2 [244], IFNG (interferon gamma) [245], NUCKS1 [246], CTBP1 [247], DNAJC3 [180], ATP6 [248], BRD4 [249], EIF4B [250], COX2 [251], SFPQ (splicing factor proline and glutamine rich) [252], PCBP1 [253], RPL5 [254], HSP90AB1 [255], TRA2A […”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

Vastrad¹,

Vastrad²

2022

Preprint

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Type 1 diabetes mellitus (T1DM) comprise the most common forms of autoimmune disease. The aim of this investigation was to apply a bioinformatics approach to reveal related pathways or genes involved in the development of T1DM. The next generation sequencing (NGS) dataset GSE182870 was downloaded from the gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis was performed using DESeq2. The g:Profiler was utilized to analyze the functional enrichment, gene ontology (GO) and REACTOME pathway of the differentially expressed genes. Protein-protein interaction (PPI) network, modules, miRNA-hub gene regulatory network, and TF-hub gene regulatory network were conducted via comprehensive target prediction and network analyses. Finally, hub genes were validated by using receiver operating characteristic curve analysis. A total of 860 DEGs were screened out from NGS dataset, among which 477 genes were up regulated and 383 genes were down regulated. GO enrichment analysis indicated that up regulated genes were mainly involved in cellular metabolic process, intracellular anatomical structure and catalytic activity, and the down regulated genes were significantly enriched in cellular nitrogen compound biosynthetic process, protein containing complex and heterocyclic compound binding. REACTOME pathway enrichment analysis showed that the up regulated genes were mainly enriched in metabolism of carbohydrates and the down regulated genes were significantly enriched in metabolism of RNA. A PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed, and hub genes (MAPK14, RHOC, MAD2L1, TAF1, TRAF2, HSP90AA1, TP53, HSP90AB1, UBA52 and RACK1) were identified. This study provides further insights into the underlying pathogenesis of T1DM.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

Vastrad¹,

Vastrad²

2022

Preprint

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“…Aspartyl peptidase CatD degrades both Aβ [ 253 , 254 , 255 ] and tau [ 256 , 257 ] and is strongly implicated in the pathogenesis of AD [ 258 ]. In AD patients, CatD levels are high in cortical and hippocampal neurons [ 259 ], amyloid plaques, and cerebrospinal fluid [ 260 , 261 , 262 ]. It has been suggested that CatD is also involved in the proteolysis of both lipid‐free recombinant full‐length human apolipoprotein E (apoE) and lipidated human plasma full‐length apoE4 into toxic peptide, contributing to the progression of AD [ 263 ].…”

Section: Lysosomal Peptidases In Neurodegenerationmentioning

confidence: 99%

Lysosomal peptidases—intriguing roles in cancer progression and neurodegeneration

et al. 2022

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Lysosomal peptidases are hydrolytic enzymes capable of digesting waste proteins that are targeted to lysosomes via endocytosis and autophagy. Besides intracellular protein catabolism, they play more specific roles in several other cellular processes and pathologies, either within lysosomes, upon secretion into the cell cytoplasm or extracellular space, or bound to the plasma membrane. In cancer, lysosomal peptidases are generally associated with disease progression, as they participate in crucial processes leading to changes in cell morphology, signaling, migration, and invasion, and finally metastasis. However, they can also enhance the mechanisms resulting in cancer regression, such as apoptosis of tumor cells or antitumor immune responses. Lysosomal peptidases have also been identified as hallmarks of aging and neurodegeneration, playing roles in oxidative stress, mitochondrial dysfunction, abnormal intercellular communication, dysregulated trafficking, and the deposition of protein aggregates in neuronal cells. Furthermore, deficiencies in lysosomal peptidases may result in other pathological states, such as lysosomal storage disease. The aim of this review was to highlight the role of lysosomal peptidases in particular pathological processes of cancer and neurodegeneration and to address the potential of lysosomal peptidases in diagnosing and treating patients.

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“…Furthermore, a recent study indicates that cathepsin D may be a peripheral AD biomarker. Plasma cathepsin D levels quantified by immunoblotting and ELISA were found to be decreased in human subjects with amyloid plaque deposition compared to the control group [ 108 ]. In addition, the plasma cathepsin D level was negatively correlated with clinical dementia rating scale sum of boxes (CDR-SB) scores.…”

Section: α-Synuclein Cleavage By Cathepsin Dmentioning

confidence: 99%

“…In addition, the plasma cathepsin D level was negatively correlated with clinical dementia rating scale sum of boxes (CDR-SB) scores. Furthermore, an integrated multivariable logistic regression model using plasma cathepsin D levels allowed the discrimination of AD from non-AD [ 108 ].…”

Section: α-Synuclein Cleavage By Cathepsin Dmentioning

confidence: 99%

Proteolytic α-Synuclein Cleavage in Health and Disease

Bluhm

Schrempel

Hörsten

et al. 2021

IJMS

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In Parkinson’s disease, aggregates of α-synuclein within Lewy bodies and Lewy neurites represent neuropathological hallmarks. However, the cellular and molecular mechanisms triggering oligomeric and fibrillary α-synuclein aggregation are not fully understood. Recent evidence indicates that oxidative stress induced by metal ions and post-translational modifications such as phosphorylation, ubiquitination, nitration, glycation, and SUMOylation affect α-synuclein conformation along with its aggregation propensity and neurotoxic profiles. In addition, proteolytic cleavage of α-synuclein by specific proteases results in the formation of a broad spectrum of fragments with consecutively altered and not fully understood physiological and/or pathological properties. In the present review, we summarize the current knowledge on proteolytical α-synuclein cleavage by neurosin, calpain-1, cathepsin D, and matrix metalloproteinase-3 in health and disease. We also shed light on the contribution of the same enzymes to proteolytical processing of pathogenic proteins in Alzheimer’s disease and report potential cross-disease mechanisms of pathogenic protein aggregation.

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Identification of Cathepsin D as a Plasma Biomarker for Alzheimer’s Disease

Cited by 22 publications

References 59 publications

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

Bioinformatics Analysis of next generation sequencing data for Risk Prediction in Patients with Type 1 diabetes mellitus

Lysosomal peptidases—intriguing roles in cancer progression and neurodegeneration

Proteolytic α-Synuclein Cleavage in Health and Disease

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