SNCA (Synuclein Alpha)

This study is the first to integrate bibliometric and bioinformatics methods, revealing the macro-level trends in OP-ATG research and the molecular mechanisms underlying OP-LP crossover. It successfully identified five key OP-LP targets, providing a new perspective for understanding OP mechanisms and developing targeted therapies.

Elucidating the underlying mechanisms could inform the creation of innovative treatments designed to slow or alter the trajectory of PD. The present study emphasizes the potential benefits of AC with contemporary scientific investigation to address the unmet needs of patients suffering from PD.

In an effort to elucidate how α-syn bridges melanomagenesis and the neurodegenerative events of PD, this review discusses specific cellular and molecular pathways related to α-syn proteostasis, including environmental factors implicated in melanocytic transformation, such as UV radiation. Addressing open questions and establishing novel experimental models remain essential for developing effective therapeutic approaches to target melanoma and PD without overlooking their comorbidity.

MB also significantly reduced H2O2-induced early (1h) ROS production in the cytosol and mitochondria and the expression of oxidative stress and modified antioxidant-related proteins, including Nuclear factor erythroid 2-related factor 2 (NRF2), affiliated Kelch-like ECH-associated protein 1 (KEAP1), Heme Oxygenase 1 (HO1), and Adenosine Monophosphate-Activated Protein Kinase (AMPK) after 3h exposure. Our current data suggest a novel glioprotective role for MB in MSA pathology, specifically against H2O2-mediated oxidative injury, and invite future work to investigate MB glioprotection in other in vivo MSA models.

Firstly, the dual pathway specific enrichment strategy of O-GlcNAc modified peptides and N-glycosylated peptides was applied to ferroptosis study for the first time, which realized a systematic analysis of glycosylation patterns in the process of cell death. Secondly, high-resolution mass spectrometry combined with multi-platform data processing (MaxQuant/PEAKS) was used to deeply integrate transcriptomes and single-cell transcriptomes to construct a panoramic analysis framework with multi-omics mutual evidence. Thirdly, Scissor method was introduced to map TCGA ferroptosis pathway activity to single-cell data to achieve cross-scale analysis from population level to cell subsets. Fourth, combined with multi-dimensional bioinformatics tools, the characteristics of modification sites, subcellular localization, protein interaction network and functional pathway were annotated. Fifth, on the basis of multi-omics results, double-layer validation by qPCR and Western Blot at the transcriptional and protein levels significantly improved the credibility of the research conclusions. Its limitations are that the research mainly relies on high-throughput omics and computational analysis, and lacks systematic in vitro and in vivo functional verification and combination drug sensitivity experiments, as well as the support of real-world clinical cohorts.

These findings suggest that Netrin-1 protects dopaminergic neurons by regulating neuroinflammation, preserving DRD2 signaling, and inhibiting phosphorylation of GSK3β at Tyr216, thereby offering potential as a therapeutic agent for dopaminergic neurodegeneration.

Among twenty hub genes, eight key FRDEGs, including activating transcription factor 3 (ATF3), Enhancer of zeste homolog 2 (EZH2), synuclein alpha (SNCA), prostaglandin-endoperoxide synthase 2 (PTGS2), NADPH oxidase 4 (NOX4), cyclin-dependent kinase inhibitor 2A (CDKN2A), sequestosome 1 (SQSTM1), and interleukin 6 (IL6), were similarly regulated across external datasets, and the expression of these genes was also confirmed by qRT-PCR. These findings highlight the pivotal role of these genes in MSCs aging and ferroptosis, suggesting that targeting them could enhance MSCs regenerative capacity and mitigate the progression of aging-related alterations in MSCs.

These suggest that SNCA+ cells are significant poor prognostic factors in nivolumab therapy for advanced GC. Targeting SNCA may be a promising strategy to improve clinical outcomes in anti-PD1/PDL1 therapy for GC.

The atypical neuropathological features observed, which are reminiscent of those observed for the G51D aSyn variant, suggest a causal role of the SNCA variant with a distinct clinical and pathological phenotype, which is further supported by the properties of the mutant aSyn.

Our Plp1-tTA::tetO-SNCA*A53T transgenic (Tg) mice express mutant human A53T α-syn in oligodendrocytes after dietary doxycycline withdrawal at 8 weeks of age; they typically develop progressive ataxia around 22 weeks and die by 30 weeks...In human MSA-C, distinct distribution patterns between α-syn oligomers and p-α-syn deposits were also observed. Thus, increased sharing of α-syn oligomers via preserved Cx gap junctions may help attenuate MSA-C pathology by reducing neuronal α-syn aggregates.

However, NF-κ B signaling pathway inhibitor BAY11-7082 improved the above indicators. Animal studies revealed that TMAO induced intracranial inflammation, affected the expression of functional proteins in the cerebral lymphatic system, and intensified SNCA aggregation in the mouse brain. TMAO can activate the NF-κB signaling pathway and damage the cellular function of brain glymphatic system and meningeal lymphatic vessels, and promote intracranial inflammation and SNCA deposition in mice, which may be a potential mechanism for TMAO involvement in neurodegenerative diseases.

α-Syn-induced NTN1 reduction exacerbates early PD pathology by impairing axonal and synaptic integrity, while NTN1 restoration mitigates these effects, suggesting therapeutic potential. These findings emphasize axon guidance pathways as key contributors to PD pathogenesis and targets for disease-modifying strategies.