Characterization of gene expression profiles in Alzheimer’s disease and osteoarthritis: A bioinformatics study

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0316708 - e0316708

Published: Feb. 7, 2025

Alzheimer's disease (AD) and Osteoarthritis (OA) have been shown to a close association in previous studies, but the pathogenesis of both diseases are unclear. This study explores potential common molecular mechanisms between AD OA through bioinformatics analysis, providing new insights for clinical treatment strategies. The OA-related datasets were downloaded from gene expression database GEO. analyzed obtain differentially expressed (DEG) AD, respectively. intersection these DEGs was identify (Co-DEGs). Subsequently, Co-DEGs enriched, protein-protein interaction network constructed core genes. genes validated separate dataset, their diagnostic value analyzed. In addition, using set enrichment analysis single-gene genome variation analysis. Analysis on chips patients revealed significant changes patterns. Notably, EFEMP2 TSPO, associated with inflammatory responses, showed lower levels patients, suggesting downregulation pathological backgrounds diseases. Additionally, GABARAPL1, which is crucial maturation autophagosomes, found be upregulated conditions. These findings suggest as biomarkers therapeutic targets. However, confirm effectiveness targets, more in-depth mechanistic studies needed future, particularly explore feasibility specific combating progression by regulating suggests that shares mechanisms. identification EFEMP2, TSPO key target highlights factors Further investigation into could lead candidate targets directions OA, offering promising avenues developing effective targeted interventions.

Language: Английский

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Insights into the differential role of GABARAPs proteins at the proteomic level

Hämostaseologie, Journal Year: 2024, Volume and Issue: 44

Published: Feb. 1, 2024

Introduction Through the route of conventional secretory pathway, FVIII is synthesized into ER, folded and transported Golgi by interacting with chaperones cargo proteins [1]. The mammalian family ATG8 proteins, comprising GABARAP, GABARAPL1 GABARAPL2, are currently being highly studied for their versatile roles in processes such as signaling, vesicular trafficking autophagy [2]. We previously created CRISPR-cas9 knockouts these genes observed that GABARAP SKO decreased secretion (by 25%), GABARAPL2 increased 50-100%). also a cumulative effect upon performing DKOs (GABARAP-GABARAPL1 35%, GABARAP-GABARAPL2 95%; GABARAPL1-L2 70%) TKOs (increase 30%). Therefore, despite subtle differences, they appear to play distinct may be hard distinguish due high homology cellular vesicle complexity.

Language: Английский

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A new cellular platform for studying autophagy

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 29, 2024

Abstract Atg8 proteins play a crucial role in autophagy. There is single isoform yeast, while mammals have up to seven homologs categorized into LC3s and GABARAPs. The GABARAP subfamily consists of GABARAP, GABARAPL1, GABARAPL2/GATE16, implicated various stages along the pathway. However, intricacies among are complex require more precise delineation. Here, we introduce new cellular platform study autophagy using CRISPR/Cas9-mediated tagging endogenous genes with different fluorescent proteins. This allows robust examination by flow cytometry cell populations monitoring at single-cell resolution fluorescence microscopy. Strikingly, simultaneous labeling GABARAPs identification isolation autophagosomes differentially marked these Using this system, found that associated autophagosomes. We argue will be studying unique roles individual other putative processes.

Language: Английский

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Plasma Proteomic Signature of Mucolipidosis Type IV

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 29, 2024

Abstract Mucolipidosis IV (MLIV) is an autosomal-recessive pediatric disease that leads to motor and cognitive deficits loss of vision. It caused by the function lysosomal channel transient receptor potential mucolipin-1, TRPML1, associated with early brain phenotype consisting glial reactivity, hypomyelination, abnormalities, increased cytokine expression. Although field approaching first translationally relevant therapy, we currently lack a molecular signature can be used detect therapeutic efficacy. In current study, analyzed 7,322 proteins in plasma proteome compare protein profiles clinical measures severity (motor function, muscle tone, age). To do so, aptamer-based profiling on isolated from 18 MLIV patients 37 aged-matched controls biorepository. We identified total 1,961 differentially expressed between control subjects, functions spanning many major hallmarks MLIV. Our analysis revealed decrease abundance neuronal increase proteins, consistent dysfunction pathology observed patients. particular, lower levels synaptic (e.g., GABARAP) best correlated severity. Next, compared mouse model shared alterations 45 proteins. The up-regulated overlapping were largely related ACTN2, GLB1), while down-regulated myelination (e.g. TPPP3, CNTN2). Both signatures are our understanding key hallmarks: impaired modified function. Collectively, these data indicate peripheral blood mirror changes found suggest candidate markers validated future studies.

Language: Английский

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Glycophagy is involved in cardiac glycogen regulation in response to exercise

Current Research in Physiology, Journal Year: 2024, Volume and Issue: 7, P. 100131 - 100131

Published: Jan. 1, 2024

Cardiac glycogen-autophagy ('glycophagy') is disturbed in cardiometabolic pathologies. The physiological role of cardiac glycophagy unclear. Exercise induces transient glycogen accumulation. Thus, this study experimentally examined involvement during recovery from an exhaustive exercise protocol. Peak myocardial accumulation mice was evident at 2 h post-exercise, preceded by activation synthase. At 4 and 16 degradation associated with decreased STBD1 (glycophagy tagging protein) increased GABARAPL1 (Atg8 protein), suggesting that activity increased. These findings provide the first evidence involved physiologic homeostasis post-exercise.

Language: Английский

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Differential expression of GABARAPs in GBM renders temozolomide sensitivity in a p53-dependent manner

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

Abstract Glioblastoma (GBM) is one of the most debilitating and extremely aggressive tumors, with a median survival less than year. GBMs have high metastatic potential frequently acquire chemoresistance. The current multimodal treatment approaches for GBM include surgical tumor resurrection, radiotherapy, chemotherapy but these leave patient long-term disabilities such as depletion cognitive abilities, leukoencephalopathy, recurrence in 6-8 months. Glioma cells are highly dependent on autophagy to survive proliferate. Autophagy inhibition has proven be beneficial strategy restricting glioma growth. However, pathway cannot efficiently targeted due lack specific inhibitors. Understanding vulnerabilities gene expression can help design better This study demonstrates differential GABARAP family members low-grade GBM. Our highlights response induction. Moreover, knockdown enhanced proliferation reduced temozolomide (TMZ) sensitivity glial by decreasing p53 expression. selective pattern genes utilized screen patients who might respond treatment. subtle regulation environmental cues.

Language: Английский

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Multiplex Genomic Tagging of Mammalian ATG8s to Study Autophagy

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107908 - 107908

Published: Oct. 1, 2024

Language: Английский

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