Neurotrophic factors for Parkinson's disease: Current status, progress, and remaining questions. Conclusions from a 2023 workshopBarker, Saarma, Svendsen
et alJ Parkinsons Dis (2024) 14 (8), 1659-1676
Abstract: In 2023, a workshop was organized by the UK charity Cure Parkinson's with The Michael J Fox Foundation for Parkinson's Research and Parkinson's UK to review the field of growth factors (GFs) for Parkinson's disease (PD). This was a follow up to a previous meeting held in 2019.1 This 2023 workshop reviewed new relevant data that has emerged in the intervening 4 years around the development of new GFs and better models for studying them including the merit of combining treatments as well as therapies that can be modulated. We also discussed new insights into GF delivery and trial design that have emerged from the analyses of completed GDNF trials, including the patient voice, as well as the recently completed CDNF trial.2 We then concluded with our recommendations on how GF studies in PD should develop going forward.
Regulation of N-Glycosylation of CDNF on Its Protein Stability and Function in Hypoxia/Reoxygenation Model of H9C2 CellsHuang, Dong, Jia
et alCell Biol Int (2025)
Abstract: Myocardial ischemia-reperfusion (I/R) injury is a cause of high post-interventional mortality in patients with acute myocardial infarction (MI). Cerebral dopamine neurotrophic factor (CDNF) is an endoplasmic reticulum (ER) resident protein, and its expression and secretion are induced when tissues and cells are subjected to hypoxia, ischemia, or traumatic injury. As a novel cardiomyokine, CDNF plays a crucial role in the progression of myocardial I/R injury. In our previous study, we reported that the overexpression of CDNF inhibited tunicamycin-induced H9C2 cell apoptosis. Moreover, there is a unique N-glycosylation site at Asn57 in the CDNF protein, which likely affects its function in H9C2 cells. However, the detailed impact remains unexplored. In our current study, we observed elevated levels of CDNF in the serum of acute MI patients, myocardial tissue of I/R model mice, and H/R model H9C2 cells. To detect the effect of N-glycosylation on the CDNF protein, we constructed an Asn57 mutant (N57A) plasmid and found that the N57A protein presented similar intracellular localization to those of the wild-type CDNF protein. However, the N57A protein demonstrated reduced stability, and the mutant protein could not protect H/R-induced H9C2 cells from apoptosis. Moreover, this process may occur through the downregulation of the PI3K/Akt pathway. Therefore, N-glycosylation of CDNF may be essential for protein stability and its protective role in H/R injury in H9C2 cells.© 2025 International Federation of Cell Biology.
Biotransformation of Ganoderma lucidum and Hericium erinaceus for ex vivo gut-brain axis modulation and mood-related outcomes in humans: CREB/BDNF signaling and microbiota-driven synergiesKoszła, Kukula-Koch, Jóźwiak
et alJ Ethnopharmacol (2025) 342, 119393
Abstract: The human gut microbiota plays a crucial role in various aspects of health, extending beyond digestion and nutrient absorption. Ganoderma lucidum (Reishi) and Hericium erinaceus (Lion's Mane), traditional medicinal mushrooms, have garnered interest due to their potential to exert positive health effects. The aim of our study was to investigate the molecular impact of Reishi and Lion's Mane on mood regulation through the gut-brain axis.We utilized a dynamic simulator of the human intestinal microbial ecosystem (SHIME), followed by HPLC-ESI-QTOF-MS/MS and a series of biochemical and molecular assays, including MTT for cell viability, fluorogenic probes for redox balance (ROS and GSH), and Western blot for protein analysis.Chromatographic analysis confirmed the presence of bioactive compounds in both mushrooms, including triterpenoids (ganoderic acids) and polysaccharides in G. lucidum, as well as hericenones and erinacines in H. erinaceus. We observed concentration-dependent changes in metabolic activity and redox balance due to microbiome cell-free supernatant treatment (M-CFSs). M-CFSs also influenced the Nrf2 pathway and activated heat shock proteins, which may confer neuroprotective effects. Notably, M-CFSs upregulated neurotrophic factors such as BDNF, CDNF, and MANF, crucial for neuronal function. Our study revealed alterations in intracellular signaling cascades, most notably the CREB/BDNF pathway. Moreover, the Akt/mTOR and ERK1/2 showed no significant changes, while Akt/GSK3α/β displayed only partial modifications. The overlapping effects of synaptic activity and activation of the gut-brain axis appear to contribute to mood enhancement.These pilot findings suggest a potential role for G. lucidum and H. erinaceus in mood disorder regulation through multifaceted mechanisms involving the gut microbiota. The study underscores the importance of understanding the synergistic interactions between medicinal fungi, gut microbiota, and neural processes to develop novel or preventive strategies for mental health disorders.Copyright © 2025 Elsevier B.V. All rights reserved.
Identifying Significant SNPs of the Total Number of Piglets Born and Their Relationship with Leg Bumps in PigsBakoev, Getmantseva, Kolosova
et alBiology (Basel) (2024) 13 (12)
Abstract: The aim of this study was to identify genetic variants and pathways associated with the total number of piglets born and to investigate the potential negative consequences of the intensive selection for reproductive traits, particularly the formation of bumps on the legs of pigs. We used genome-wide association analysis and methods for identifying selection signatures. As a result, 47 SNPs were identified, localized in genes that play a significant role during sow pregnancy. These genes are involved in follicle growth and development (SGC), early embryonic development (CCDC3, LRRC8C, LRFN3, TNFRSF19), endometrial receptivity and implantation (NEBL), placentation, and embryonic development (ESRRG, GHRHR, TUSC3, NBAS). Several genes are associated with disorders of the nervous system and brain development (BCL11B, CDNF, ULK4, CC2D2A, KCNK2). Additionally, six SNPs are associated with the formation of bumps on the legs of pigs. These variants include intronic variants in the CCDC3, ULK4, and MINDY4 genes, as well as intergenic variants, regulatory region variants, and variants in the exons of non-coding transcripts. The results suggest important biological pathways and genetic variants associated with sow fertility and highlight the potential negative impacts on the health and physical condition of pigs.
膜杰作
Star Staining
