Parkinson's disease(PD)is a neurodegenerative disorder characterized by the aggregation ofα-synuclein(α-syn)and dysregulated synaptic vesicle(SV)recycling.Emerging evidence suggests that ferroptosis is the targe...Parkinson's disease(PD)is a neurodegenerative disorder characterized by the aggregation ofα-synuclein(α-syn)and dysregulated synaptic vesicle(SV)recycling.Emerging evidence suggests that ferroptosis is the target of PD therapy.However,the identification of effective anti-ferroptosis treatments remains elusive.This study explores the therapeutic potential of low-intensity ultrasound(US)in modulating SV recycling and anti-ferroptosis in cellular and animal models of PD.We demonstrate that optimized US stimulation(610 kHz,0.2 W/cm2)activates Piezo1 channel-mediated fast endophilin-mediated endocytosis,which promotes SV recycling and synaptic function,presenting with increased frequency and amplitude of both spontaneous excitatory synaptic currents and miniature excitatory postsynaptic currents.Repaired SV recycling in turn reduces the accumulation ofα-syn expression and ferroptotic cell death.These findings support the potential of noninvasive ultrasonic neuromodulation as a therapeutic strategy for PD and lead to meaningful health outcomes for the aging population.展开更多
Main text Alzheimer’s disease(AD),the most prevalent form of dementia,is characterized by deposits of two abnormal proteins,namely amyloid-β(Aβ)and tau,in the brain.There is growing evidence for the clinical signif...Main text Alzheimer’s disease(AD),the most prevalent form of dementia,is characterized by deposits of two abnormal proteins,namely amyloid-β(Aβ)and tau,in the brain.There is growing evidence for the clinical significance of plasma phosphorylated tau(p-tau)assays in detecting AD pathology[1,2],similar to CSF and positron emission tomography(PET)biomarkers.Currently available immunoassays for plasma p-tau detect C-terminally truncated p-tau containing the N-terminus to the mid-domain(N-p-tau)[2].展开更多
Oral microbiota is the second largest microbial colony in the body and forms a complex ecological community that influences oral and brain health.Impaired homeostasis of the oral microbiota can lead to pathological ch...Oral microbiota is the second largest microbial colony in the body and forms a complex ecological community that influences oral and brain health.Impaired homeostasis of the oral microbiota can lead to pathological changes,resulting in central nervous system(CNS)diseases.However,the mechanisms and clinical value of how the oral microbiome influences the brain remain unclear.This review summarizes recent clinical findings on the role of the oral microbiota in CNS diseases and proposes potential approaches to understand the way the oral microbiota and brain communicate.We propose three underlying patterns involving neuroinflammation,neuroendocrine regulation,and CNS signaling between oral microbiota and CNS diseases.We also summarize the clinical characteristics and potential utilization of the oral microbiota in ischemic stroke,Alzheimer's and Parkinson's disease,intracranial aneurysms,and mental disorders.Although the current findings are preliminary and clinical evidence is incomplete,oral microbiota is a potential biomarker for the clinical diagnosis and treatment of CNS diseases.展开更多
基金supported by the National Science Found for Young Scientists of China(82101339 and 22206051)the General Program of Natural Science Fund of Jiangsu Province(BK20221205)the General Program of Natural Science Research of Jiangsu Higher Education Institutions of China(20 KJB320034).
文摘Parkinson's disease(PD)is a neurodegenerative disorder characterized by the aggregation ofα-synuclein(α-syn)and dysregulated synaptic vesicle(SV)recycling.Emerging evidence suggests that ferroptosis is the target of PD therapy.However,the identification of effective anti-ferroptosis treatments remains elusive.This study explores the therapeutic potential of low-intensity ultrasound(US)in modulating SV recycling and anti-ferroptosis in cellular and animal models of PD.We demonstrate that optimized US stimulation(610 kHz,0.2 W/cm2)activates Piezo1 channel-mediated fast endophilin-mediated endocytosis,which promotes SV recycling and synaptic function,presenting with increased frequency and amplitude of both spontaneous excitatory synaptic currents and miniature excitatory postsynaptic currents.Repaired SV recycling in turn reduces the accumulation ofα-syn expression and ferroptotic cell death.These findings support the potential of noninvasive ultrasonic neuromodulation as a therapeutic strategy for PD and lead to meaningful health outcomes for the aging population.
基金supported in part by AMED under Grant Numbers JP18dm0207018,JP19dm0207072,JP18dk0207026,JP19dk0207049,21wm0425015,21dm0307003,22dk0207055MEXT KAKENHI under Grant Numbers JP16H05324 and JP18K07543+1 种基金JST under Grant Numbers JPMJCR1652 and JPMJMS2024the Kao Research Council for the Study of Healthcare Science,Biogen Idec Inc.and APRINOIA Therapeutics.
文摘Main text Alzheimer’s disease(AD),the most prevalent form of dementia,is characterized by deposits of two abnormal proteins,namely amyloid-β(Aβ)and tau,in the brain.There is growing evidence for the clinical significance of plasma phosphorylated tau(p-tau)assays in detecting AD pathology[1,2],similar to CSF and positron emission tomography(PET)biomarkers.Currently available immunoassays for plasma p-tau detect C-terminally truncated p-tau containing the N-terminus to the mid-domain(N-p-tau)[2].
基金National Natural Science Foundation of China,Grant/Award Number:82301715Wuxi Taihu Lake Talent Plan,Supports for Leading Talents in Medical and Health Profession,Grant/Award Number:2020THRC-DJ-SNW+1 种基金Jiangsu Province Double-Creation Doctoral Talent Plan,Grant/Award Number:JSSCBS20221995WuXi Municipal Health Commission,Grant/Award Number:Q202222。
文摘Oral microbiota is the second largest microbial colony in the body and forms a complex ecological community that influences oral and brain health.Impaired homeostasis of the oral microbiota can lead to pathological changes,resulting in central nervous system(CNS)diseases.However,the mechanisms and clinical value of how the oral microbiome influences the brain remain unclear.This review summarizes recent clinical findings on the role of the oral microbiota in CNS diseases and proposes potential approaches to understand the way the oral microbiota and brain communicate.We propose three underlying patterns involving neuroinflammation,neuroendocrine regulation,and CNS signaling between oral microbiota and CNS diseases.We also summarize the clinical characteristics and potential utilization of the oral microbiota in ischemic stroke,Alzheimer's and Parkinson's disease,intracranial aneurysms,and mental disorders.Although the current findings are preliminary and clinical evidence is incomplete,oral microbiota is a potential biomarker for the clinical diagnosis and treatment of CNS diseases.
