Artemisinin,also called qinghaosu,is originally derived from the sweet wormwood plant(Artemisia annua),which is used in traditional Chinese medicine.Artemisinin and its derivatives(artemisinins)have been widely used f...Artemisinin,also called qinghaosu,is originally derived from the sweet wormwood plant(Artemisia annua),which is used in traditional Chinese medicine.Artemisinin and its derivatives(artemisinins)have been widely used for many years as anti-malarial agents,with few adverse side effects.Interestingly,evidence has recently shown that artemisinins might have a therapeutic value for several other diseases beyond malaria,including cancers,inflammatory diseases,and autoimmune disorders.Neurodegeneration is a challenging age-associated neurological disorder characterized by deterioration of neuronal structures as well as functions,whereas neuroinflammation has been considered to be an underlying factor in the development of various neurodegenerative disorders,including Alzheimer’s disease.Recently discovered properties of artemisinins suggested that they might be used to treat neurodegenerative disorders by decreasing oxidation,inflammation,and amyloid beta protein(Aβ).In this review,we will introduce artemisinins and highlight the possible mechanisms of their neuroprotective activities,suggesting that artemisinins might have therapeutic potential in neurodegenerative disorders.展开更多
Alzheimer’s disease(AD),the most common dementia,is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein,and their deposition as amyloid plaques and neurofibrillary tangles(NFTs).Tau agg...Alzheimer’s disease(AD),the most common dementia,is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein,and their deposition as amyloid plaques and neurofibrillary tangles(NFTs).Tau aggregation also occurs in other common neurodegenerative diseases.Frontotemporal dementia(FTD)can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation,which may cause neuronal dysfunction and deposition of NFTs.17-allylamino-17-demethoxygeldanamycin(17-AAG)is a potent inhibitor of heat shock protein 90(Hsp90),a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins.17-AAG binds to Hsp90 and enhances degradation of Hsp90 client protein.We sought to determine whether 17-AAG can reduce Aβ and tau pathology in the brains of AD and FTD model mice expressing Aβ or P301L mutant tau,respectively.Mice were randomized to receive 25,5,or 0 mg/kg 17-AAG thrice weekly from age eight to 11 months.Analysis was performed by rotarod test on motor function,on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections,and on mortality.A high dose of 17-AAG tended to decrease NFTs in male mice(p=0.08).Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation.展开更多
基金supported by the Natural Science Foundation of Beijing of China,No.7192235(to LKX)
文摘Artemisinin,also called qinghaosu,is originally derived from the sweet wormwood plant(Artemisia annua),which is used in traditional Chinese medicine.Artemisinin and its derivatives(artemisinins)have been widely used for many years as anti-malarial agents,with few adverse side effects.Interestingly,evidence has recently shown that artemisinins might have a therapeutic value for several other diseases beyond malaria,including cancers,inflammatory diseases,and autoimmune disorders.Neurodegeneration is a challenging age-associated neurological disorder characterized by deterioration of neuronal structures as well as functions,whereas neuroinflammation has been considered to be an underlying factor in the development of various neurodegenerative disorders,including Alzheimer’s disease.Recently discovered properties of artemisinins suggested that they might be used to treat neurodegenerative disorders by decreasing oxidation,inflammation,and amyloid beta protein(Aβ).In this review,we will introduce artemisinins and highlight the possible mechanisms of their neuroprotective activities,suggesting that artemisinins might have therapeutic potential in neurodegenerative disorders.
基金This work was supported by Alzheimer’s Drug Discovery Foundation grant 271217 AFTD.
文摘Alzheimer’s disease(AD),the most common dementia,is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein,and their deposition as amyloid plaques and neurofibrillary tangles(NFTs).Tau aggregation also occurs in other common neurodegenerative diseases.Frontotemporal dementia(FTD)can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation,which may cause neuronal dysfunction and deposition of NFTs.17-allylamino-17-demethoxygeldanamycin(17-AAG)is a potent inhibitor of heat shock protein 90(Hsp90),a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins.17-AAG binds to Hsp90 and enhances degradation of Hsp90 client protein.We sought to determine whether 17-AAG can reduce Aβ and tau pathology in the brains of AD and FTD model mice expressing Aβ or P301L mutant tau,respectively.Mice were randomized to receive 25,5,or 0 mg/kg 17-AAG thrice weekly from age eight to 11 months.Analysis was performed by rotarod test on motor function,on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections,and on mortality.A high dose of 17-AAG tended to decrease NFTs in male mice(p=0.08).Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation.
