
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Ноя. 6, 2024
Язык: Английский
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Ноя. 6, 2024
Язык: Английский
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Фев. 28, 2024
Abstract Background Observational studies indicate a strong association between most neurodegenerative disorders and cathepsin, although the causative link remains unclear. Methods This research utilized Mendelian Randomization (MR) with genetic markers linked to cathepsins as instrumental variables, analyzed public Genome-Wide Association Studies (GWASs) summary data of individuals European ancestry for Alzheimer's disease (AD), Parkinson's (PD), dementia Lewy bodies (DLB) outcomes. The study applied inverse variance-weighted (IVW) method assess causal effects on AD, PD, DLB. Several sensitivity analyses heterogeneity test were conducted evaluate effectiveness results. Confounding variables accounted using multivariable MR (MVMR). Additionally, reverse was done improve forward analysis. Lastly, we utilize Bayesian Weighted (BWMR) further validate robustness Results investigation found an cathepsin H AD DLB risk. However, there negative correlation PD risk B levels. Effect estimates in MVMR BWMR remained constant. According analysis, decreased levels, negatively correlated Z no relationship cathepsins. Conclusion While higher levels associated risk, bidirectional B. By studying how influences development advancement DLB, novel methods diagnosis treatment might be investigated.
Язык: Английский
Процитировано
0Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Апрель 5, 2024
Abstract Background The pathogenesis of idiopathic pulmonary fibrosis (IPF) is complex and difficult to diagnose treat clinically. Cathepsins are involved in various physiological pathological processes, observational studies have shown an association between cathepsins IPF. However, the causal relationship them remains uncertain. Our aim was assess Methods Protein quantitative trait loci (pQTL) data for were obtained from INTERVAL studies, summary statistics IPF genome-wide (GWAS) FinnGen R10 study. Univariable Mendelian randomization (UVMR), multivariable (MVMR), data-based (SMR) Bayesian colocalization analysis conducted this Results UVMR indicated that elevated cathepsin H levels reduced overall risk (OR = 0.885,95%CI 0.827 ~ 0.947, P 3.86×10 − 4). MVMR showed effect on still present after adjusting interaction 0.895,95%CI 0.834 0.961, 0.002). In addition, SMR also suggested a 0.800,95%CI 0.699 0.916, 0.001). Finally, we validated results using UK Biobank Pharma Proteomics Project (UKB-PPP) dataset 0.897,95%CI 0.836 0.963, 0.003). Conclusions This study suggests has protective may serve as potential therapeutic target IPF, providing inspiration guidance diagnosis treatment
Язык: Английский
Процитировано
0Scientific Reports, Год журнала: 2024, Номер 14(1)
Опубликована: Июль 30, 2024
Osteoarthritis (OA) is a chronic disease due to the deterioration of cartilage structure and function, involving progressive degradation extracellular matrix. Cathepsins, lysosomal cysteine proteases, play pivotal roles in various biological pathological processes, particularly protein degradation. Excess cathepsins levels are reported contribute development OA. However, causal relationship between cathepsin family knee hip OA remains uncertain. Therefore, this study utilized bidirectional Mendelian Randomization (MR) analyses explore association. Our results indicated that elevated serum O increase overall risk OA, while increased H enhance Conversely, reverse MR did not reveal them. In summary, different anatomical locations may genetically result from elevations isoforms, which could be as diagnostic therapeutic targets clinical practice.
Язык: Английский
Процитировано
0BMC Psychiatry, Год журнала: 2024, Номер 24(1)
Опубликована: Окт. 31, 2024
Bipolar disorder is a psychiatric condition characterized by the coexistence of depression and mania. Diagnosis this can be challenging due to limited pathologic experimental tools. Treatment compliance often poor medication side effects. Although cathepsin known play significant role in diseases such as tumors osteoporosis, its disorders not yet fully understood.
Язык: Английский
Процитировано
0Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Ноя. 6, 2024
Язык: Английский
Процитировано
0