2x new MANF articles, big summary update one out o

2x new MANF articles, big summary update one out of China that you'll want the full text for, and another acute lung injury. A reminder this remains another record year in a row for MANF studies.

1) Unlocking the promise of MANF in diseases: Mechanistic insights and therapeutic potentials
Lingling Yuan et al. Mol Biol Rep. 2024.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a ubiquitous neurotrophic factor that exhibits a variety of physiological functions and plays a critical role in the exploitation of therapeutic potential across a range of diseases, including cardiovascular disorders, nervous system diseases, metabolic imbalances, and cancers. In the context of cardiac diseases, MANF significantly promotes cardiomyocyte survival and improves cardiac functionality. Furthermore, MANF not only provides neuroprotection by shielding neurons from damage and promoting nerve regeneration in neurological disorders, but also involves in insulin resistance, lipid metabolism disturbances and fat-containing liver lesions. However, the oncogenic or tumor suppressive function of MANF in cancer remains unclear, requiring further investigation to elucidate its precise role in the process of cancer initiation and progression. This review aims to summarize the latest advancements in understanding the molecular pathways, intricate mechanisms, and therapeutic potential of MANF in the prevention and treatment of various diseases, emphasizing its multifaceted contributions to health and disease management.

https://pubmed.ncbi.nlm.nih.gov/39549080/

2) MANF inhibits NLRP3 inflammasome activation by competitively binding to DDX3X in paraquat-stimulated alveolar macrophages

NLRP3 inflammasome activation in macrophages is involved in paraquat-induced acute lung injury (ALI). MANF exerts an inhibitory effect against inflammation and cell death. The aim of this study was to investigate the role of MANF in paraquat-stimulated alveolar macrophages and the potential mechanism. Paraquat-induced ALI mouse model was established by intraperitoneally injection of 30 mg/kg of paraquat. The lung pathological changes were observed by hematoxylin and eosin staining. The expression of MANF/DDX3X/NLRP3/Caspase-1 in mice lung macrophages was evaluated by double immunofluorescence staining and western blot. NLRP3 inflammasome activation and pro-inflammatory cytokines (IL-1β and IL-18) in paraquat-stimulated macrophage transfected with MANF overexpression plasmid (pcDNA3.1-MANF) or siRNA-MANF were measured by Western blot. The protein-protein interaction of MANF/DDX3X/NLRP3 was verified by Co-immunoprecipitation. As a result, MANF/DDX3X/NLRP3/Caspase-1 were upregulated in alveolar macrophages of paraquat-induced ALI in mice. In paraquat-stimulated alveolar macrophages, upregulation of MANF and DDX3X were also observed, accompanied by NLRP3 inflammasome activation. In addition, overexpression of MANF inhibited NLRP3 inflammasome activation in paraquat-stimulated alveolar macrophages. In contrast, knockdown of MANF aggravated NLRP3 inflammasome activation. Co-immunoprecipitation results revealed that DDX3X could bind to MANF and NLRP3, but MANF could not bind to NLRP3 in paraquat-stimulated alveolar macrophages. Furthermore, Co-immunoprecipitation of truncated three fragments of DDX3X confirmed MANF can interact with the helicase core of DDX3X which is the binding site for NLRP3. Taken together, MANF exerted a protective effect against paraquat-induced cytotoxicity by inhibiting the NLRP3 inflammasome activation in macrophages via competitive binding to the helicase core of DDX3X.

https://pubmed.ncbi.nlm.nih.gov/39547060/