Exploring the triad: VPS35, neurogenesis, and neurodegenerative diseases.

Vacuolar protein sorting 35 (VPS35), a critical component of the retromer complex, plays a pivotal role in the pathogenesis of neurodegenerative diseases (NDs). It is involved in protein transmembrane sorting, facilitating the transport from endosomes to the trans-Golgi network (TGN) and plasma membrane. Recent investigations have compellingly associated mutations in the VPS35 gene with neurodegenerative disorders such as Parkinson's and Alzheimer's disease. These genetic alterations are implicated in protein misfolding, disrupted autophagic processes, mitochondrial dysregulation, and synaptic impairment. Furthermore, VPS35 exerts a notable impact on neurogenesis by influencing neuronal functionality, protein conveyance, and synaptic performance. Dysregulation or mutation of VPS35 may escalate the progression of neurodegenerative conditions, underscoring its pivotal role in safeguarding neuronal integrity. This review comprehensively discusses the role of VPS35 and its functional impairments in NDs. Furthermore, we provide an overview of the impact of VPS35 on neurogenesis and further explore the intricate relationship between neurogenesis and NDs. These research advancements offer novel perspectives and valuable insights for identifying potential therapeutic targets in the treatment of NDs.

Bibliometric analysis of global research trends in magnetic resonance imaging studies of substantia nigra in Parkinson's disease (2001-2024).

Background: Parkinson's disease (PD) is a globally prevalent neurodegenerative disorder, primarily characterized by muscle rigidity, resting tremor, and bradykinesia. The incidence of PD is rapidly escalating worldwide. Numerous studies have been conducted on the application of magnetic resonance imaging (MRI) in investigating the substantia nigra (SN) in PD patients. However, to date, no bibliometric analysis has been performed on this specific research area. Therefore, this study aimed to provide a comprehensive analysis of the current status in MRI research on the SN in PD patients. Materials and methods: MRI study records related to the SN in PD patients from 2001 to 2024 were searched by using the Web of Science Core Collection (WOSCC) database and then the CiteSpace and VOSviewer were used to conduct bibliometric analysis. Results: Our analysis found that the number of published articles related studies on MRI of the SN in PD showed an overall upward trend over the past decade, in which Lehericy, Stephane, Du, Guangwei, and Huang, Xuemei are the top three authors with the most articles. Additionally, United States, China and Germany are the main contributors to MRI studies of SN in PD. And Shanghai Jiao Tong University, University of Florida and Seoul National University are the leading institutions in the field. Finally, the keyword analysis showed that the hotspots and trends of research in this field are mainly concentrated in quantitative susceptibility mapping, neuroimaging, and neuromelanin-sensitive MRI. Conclusion: These analysis identified the most influential authors, institutions, countries and research hotspots in the field of SN-MRI research in PD, which has reference significance for the research interest in this field and provides a new idea for PD prevention.

Exploring the potential mechanism of ginsenoside Rg1 to regulate ferroptosis in Alzheimer's disease based on network pharmacology.

OBJECTIVES: To explore the pathogenesis of Alzheimer's disease (AD), the potential targets and signaling pathways of ginsenoside Rg1 against AD were investigated by network pharmacology. METHODS: Ginsenoside Rg1 targets were identified through PubChem, PharmMapper, and Uniprot databases, while the GeneCards database was used to examine the respective targets of amyloid precursor protein (APP) and AD. Then, the common targets between ginsenoside Rg1 and APP were explored by the Venny tool, the interaction network diagram between the active components and the targets was built via Cytoscape software, as well as GO enrichment and KEGG pathway annotation analysis were performed. Furthermore, genes associated with ferroptosis were found by the GeneCards and FerrDb databases. Besides, the connection among ginsenoside Rg1, APP, ferroptosis, and AD was predicted and analyzed. Finally, the effects of ginsenosides Rg1 and liproxstain-1 on the proliferation and differentiation of APP/PS1 mice were evaluated by immunohistochemistry. RESULTS: Ginsenoside Rg1, APP, ferroptosis, and AD had 12 hub genes. GO enrichment and KEGG pathway annotation analysis showed that EGFR, SRC, protein hydrolysis, protein phosphorylation, the Relaxin pathway, and the FoxO signaling pathway play an important role in the potential mechanism of ginsenoside Rg1's under regulation of ferroptosis anti-AD through the modulation of APP-related signaling pathways. The APP/PS1 mice experiment verified that ginsenosides Rg1 and liproxstain-1 can promote the proliferation and differentiation. CONCLUSION: Ginsenoside Rg1, APP and ferroptosis may act on EGFR, SRC, the Relaxin and FoxO signaling pathways to regulate protein metabolism, protein phosphorylation and other pathways to improve AD symptoms.