The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct facto...The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.展开更多
Amyotrophic lateral sclerosis(ALS)is the most common motor neuron disease characterized by progressive loss of motor neurons in the brainstem and spinal cord.Currently,there is no cure or effective treatment for ALS a...Amyotrophic lateral sclerosis(ALS)is the most common motor neuron disease characterized by progressive loss of motor neurons in the brainstem and spinal cord.Currently,there is no cure or effective treatment for ALS and the cause of disease is unknown in the majority of ALS cases.Neuronal mitochondria dysfunction is one of the earliest features of ALS.Mitochondria are highly dynamic organelles that undergo continuous fission,fusion,trafficking and turnover,all of which contribute to the maintenance of mitochondrial function.Abnormal mitochondrial dynamics have been repeatedly reported in ALS and increasing evidence suggests altered mitochondrial dynamics as possible pathomechanisms underlying mitochondrial dysfunction in ALS.Here,we provide an overview of mitochondrial dysfunction and dynamic abnormalities observed in ALS,and discuss the possibility of targeting mitochondrial dynamics as a novel therapeutic approach for ALS.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82130037(to CH),81971122(to CH),82171323(to WL)the Natural Science Foundation of Jiangsu Province of China,No.BK20201113(to WL)。
文摘The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood flow.Mitochondria are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial dysfunction.Dysfunctional mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging cells.In response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological conditions.Specific interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid hemorrhage.This review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control mechanisms.It also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.
基金by grants from National Institutes of Health(R03AG044680,R21NS085747 and R01NS089604)Alzheimer’s Association(2014-NIRG-301299).
文摘Amyotrophic lateral sclerosis(ALS)is the most common motor neuron disease characterized by progressive loss of motor neurons in the brainstem and spinal cord.Currently,there is no cure or effective treatment for ALS and the cause of disease is unknown in the majority of ALS cases.Neuronal mitochondria dysfunction is one of the earliest features of ALS.Mitochondria are highly dynamic organelles that undergo continuous fission,fusion,trafficking and turnover,all of which contribute to the maintenance of mitochondrial function.Abnormal mitochondrial dynamics have been repeatedly reported in ALS and increasing evidence suggests altered mitochondrial dynamics as possible pathomechanisms underlying mitochondrial dysfunction in ALS.Here,we provide an overview of mitochondrial dysfunction and dynamic abnormalities observed in ALS,and discuss the possibility of targeting mitochondrial dynamics as a novel therapeutic approach for ALS.
