While many drugs are effective at reducing the relapse frequency of multiple sclerosis (MS), there is an unmet need for treatments that slow neurodegeneration resulting from secondary disease progression. The mechanis...While many drugs are effective at reducing the relapse frequency of multiple sclerosis (MS), there is an unmet need for treatments that slow neurodegeneration resulting from secondary disease progression. The mechanism of neurodegeneration in MS has not yet been established. Here, we discovered a potential pathogenetic role of ferroptosis, an iron-dependent regulated cell death mechanism, in MS. We found that critical ferroptosis proteins (acyl-CoA synthetase long-chain family member 4, ACSL4) were altered in an existing genomic database of MS patients, and biochemical features of ferroptosis, including lipid reactive oxygen species (ROS) accumulation and mitochondrial shrinkage, were observed in the experimental autoimmune encephalitis (EAE) mouse model. Targeting ferroptosis with ferroptosis inhibitors or reducing ACSL4 expression improved the behavioral phenotypes of EAE mice, reduced neuroinflammation, and prevented neuronal death. We found that ferroptosis was an early event in EAE, which may promote T-cell activation through T-cell receptor (TCR) signaling in vitro and in vivo. These data indicate that ferroptosis may be a potential target for treating MS.展开更多
A lack of convenient and reliable biomarkers for diagnosis and prognosis is a common challenge for neurodegenerative diseases such as Alzheimer's disease(AD).Recent advancement in ultrasensitive protein assays has...A lack of convenient and reliable biomarkers for diagnosis and prognosis is a common challenge for neurodegenerative diseases such as Alzheimer's disease(AD).Recent advancement in ultrasensitive protein assays has allowed the quantification of tau and phosphorylated tau proteins in peripheral plasma.Here we identified 66 eligible studies reporting quantification of plasma tau and phosphorylated tau 181(ptau181)using four ultrasensitive methods.Meta-analysis of these studies confirmed that the AD patients had significantly higher plasma tau and ptau181 levels compared with controls,and that the plasma tau and ptau181 could predict AD with high-accuracy area under curve of the Receiver Operating Characteristic Therefore,plasma tau and plasma ptau181 can be considered as biomarkers for AD diagnosis.展开更多
基金the National Natural Science Foundation of China(grant numbers 81773965 to X.H.,81873064 to DO,and 81673664 to QZ).
文摘While many drugs are effective at reducing the relapse frequency of multiple sclerosis (MS), there is an unmet need for treatments that slow neurodegeneration resulting from secondary disease progression. The mechanism of neurodegeneration in MS has not yet been established. Here, we discovered a potential pathogenetic role of ferroptosis, an iron-dependent regulated cell death mechanism, in MS. We found that critical ferroptosis proteins (acyl-CoA synthetase long-chain family member 4, ACSL4) were altered in an existing genomic database of MS patients, and biochemical features of ferroptosis, including lipid reactive oxygen species (ROS) accumulation and mitochondrial shrinkage, were observed in the experimental autoimmune encephalitis (EAE) mouse model. Targeting ferroptosis with ferroptosis inhibitors or reducing ACSL4 expression improved the behavioral phenotypes of EAE mice, reduced neuroinflammation, and prevented neuronal death. We found that ferroptosis was an early event in EAE, which may promote T-cell activation through T-cell receptor (TCR) signaling in vitro and in vivo. These data indicate that ferroptosis may be a potential target for treating MS.
基金supported by the Ministry of Science and Technology of China(2018YFC1312300)the National Natural Science Foundation of China(81722016)。
文摘A lack of convenient and reliable biomarkers for diagnosis and prognosis is a common challenge for neurodegenerative diseases such as Alzheimer's disease(AD).Recent advancement in ultrasensitive protein assays has allowed the quantification of tau and phosphorylated tau proteins in peripheral plasma.Here we identified 66 eligible studies reporting quantification of plasma tau and phosphorylated tau 181(ptau181)using four ultrasensitive methods.Meta-analysis of these studies confirmed that the AD patients had significantly higher plasma tau and ptau181 levels compared with controls,and that the plasma tau and ptau181 could predict AD with high-accuracy area under curve of the Receiver Operating Characteristic Therefore,plasma tau and plasma ptau181 can be considered as biomarkers for AD diagnosis.
