{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gong L"],"funding":["Shanghai Tenth People’s Hospital"],"pagination":["3938940"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8972155"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["2022"],"pubmed_abstract":["A part of the axonal cytoskeleton protein complex, neurofilament light chain (NF-L) has been suggested as a pathological hallmark in various neurological disorders, including hemorrhagic stroke, vascular dementia, and cerebral small vessel disease. Neuroaxonal debris are mainly engulfed and phagocytosed by microglia, while the effects of NF-L on microglia have not been elucidated. Ferritin heavy chain (FTH) not only reflects the age-related status of microglia but may also be secreted into the extracellular space. After treatment of microglia with varying concentrations of NF-L (0-3 <i>μ</i>g/ml), we found robust increases in the number of secretory FTH-containing exosomes in the medium. Induction of the FTH-containing exosomes secreted from microglia stimulates neuronal loss and membrane lipid peroxidation, as assessed by CKK8 and C11-Bodipy<sup>581/591</sup>, respectively. However, this oxidative stress damage was attenuated by blocking <i>Fth1</i> expression. Our results suggest that NF-L, as a biomarker of axonal injury itself, could participate in neuronal ferroptosis in a nonclassical manner by secreting FTH-containing exosomes from microglia into the extracellular matrix."],"journal":["Oxidative medicine and cellular longevity"],"pubmed_title":["Neurofilament Light Chain (NF-L) Stimulates Lipid Peroxidation to Neuronal Membrane through Microglia-Derived Ferritin Heavy Chain (FTH) Secretion."],"pmcid":["PMC8972155"],"funding_grant_id":["SHYCS05","shslczdzk06102","81901183"],"pubmed_authors":["Dou Y","Yu Q","Mao B","Xu C","Gong L","Wang H","Zhao Y"],"additional_accession":[]},"is_claimable":false,"name":"Neurofilament Light Chain (NF-L) Stimulates Lipid Peroxidation to Neuronal Membrane through Microglia-Derived Ferritin Heavy Chain (FTH) Secretion.","description":"A part of the axonal cytoskeleton protein complex, neurofilament light chain (NF-L) has been suggested as a pathological hallmark in various neurological disorders, including hemorrhagic stroke, vascular dementia, and cerebral small vessel disease. Neuroaxonal debris are mainly engulfed and phagocytosed by microglia, while the effects of NF-L on microglia have not been elucidated. Ferritin heavy chain (FTH) not only reflects the age-related status of microglia but may also be secreted into the extracellular space. After treatment of microglia with varying concentrations of NF-L (0-3 <i>μ</i>g/ml), we found robust increases in the number of secretory FTH-containing exosomes in the medium. Induction of the FTH-containing exosomes secreted from microglia stimulates neuronal loss and membrane lipid peroxidation, as assessed by CKK8 and C11-Bodipy<sup>581/591</sup>, respectively. However, this oxidative stress damage was attenuated by blocking <i>Fth1</i> expression. Our results suggest that NF-L, as a biomarker of axonal injury itself, could participate in neuronal ferroptosis in a nonclassical manner by secreting FTH-containing exosomes from microglia into the extracellular matrix.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022","modification":"2025-04-04T12:57:53.043Z","creation":"2025-04-04T12:57:53.043Z"},"accession":"S-EPMC8972155","cross_references":{"pubmed":["35368870"],"doi":["10.1155/2022/3938940"]}}