Background:Type 2 diabetes(T2D),but not type 1,protected against amyotrophic lateral sclerosis(ALS).In T2D serum insulin is normal or elevated in the early stages.Type 1 diabetes,characterized by a total lack of insul...Background:Type 2 diabetes(T2D),but not type 1,protected against amyotrophic lateral sclerosis(ALS).In T2D serum insulin is normal or elevated in the early stages.Type 1 diabetes,characterized by a total lack of insulin,is associated with an increased risk of ALS.The antidiabetic metformin also protects against ALS.Connexin 43(Cx43),an astrocyte protein,operates as an open channel via which toxic substances from astrocytes reach motor neurons to cause ALS.Methods:In the current study we analyzed FDA MedWatch data to determine whether insulin or metformin could reduce the risk of ALS.We performed in silico molecular docking studies and molecular dynamics simulation with Cx43 to determine if insulin or metformin dock within the Cx43 channel and can block it effectively,again reducing risk of ALS.Results:In MedWatch,Insulin use is associated with a significantly reduced risk of ALS(Proportional Reporting Ratio 0.401).Metformin use is associated with a significantly reduced risk of ALS(PRR 0.567).The Human insulin heterodimer docked within center of the Cx43 channel,effectively blocking it.Molecular dynamics simulation showed that the block is highly stable and may be responsible for the protective effect of T2D on ALS.Metformin docks within the Cx43 channel,but the relatively small size of the metformin molecule may not allow it to obstruct the passage of toxic substances from astrocytes to motor neurons.Conclusion:MedWatch data indicate that both insulin and metformin reduce risk of ALS.The results of our in silico docking study and molecular dynamics simulation corroborate our previous findings with Cx31.Insulin docks within the open hemichannel of hexameric Cx43,potentially blocking it.Molecular dynamics simulation showed that the block is stable and may be responsible for the protective effect of T2D and insulin on ALS.展开更多
The amyloid hypothesis states that the buildup ofßamyloid in the brain is the main factor for Alzheimer's disease(AD)pathogenesis.An imbalance betweenßamyloid production andß-amyloid clearance cause...The amyloid hypothesis states that the buildup ofßamyloid in the brain is the main factor for Alzheimer's disease(AD)pathogenesis.An imbalance betweenßamyloid production andß-amyloid clearance causes the advanced stages of the disease,including the development of neurofibrillary tangles containing tau protein.展开更多
In a 2012 study,occasional and low cumulative cannabis use was not associated with adverse effects on pulmonary function.'With tobacco,the more used,the more loss of air flow rate and lung volume.The same was not ...In a 2012 study,occasional and low cumulative cannabis use was not associated with adverse effects on pulmonary function.'With tobacco,the more used,the more loss of air flow rate and lung volume.The same was not true with cannabis use.Air flow rate increased rather than decreased with increased exposure to cannabis up to a certain level.展开更多
The most prevalent age-related movement condition,Parkinson's disease(PD),is characterized by bradykinesia,resting tremor,unbalanced gait,muscular rigidity,postural instability,as well as some nonmotor symptoms li...The most prevalent age-related movement condition,Parkinson's disease(PD),is characterized by bradykinesia,resting tremor,unbalanced gait,muscular rigidity,postural instability,as well as some nonmotor symptoms like autonomic and cognitive dysfunctions.展开更多
The coronavirus SARS-CoV-2 has already claimed the lives of more than six million people,according to the World Health Organization,and the actual death toll may exceed 18 million.People are avoiding severe cases of C...The coronavirus SARS-CoV-2 has already claimed the lives of more than six million people,according to the World Health Organization,and the actual death toll may exceed 18 million.People are avoiding severe cases of COvID-19 thanks to vaccines,medications,and immunity from prior infections.Yet the virus's capacity to block the body's immune response,made possible by its arsenal of proteins,is one factor in its propensity to spread.展开更多
文摘Background:Type 2 diabetes(T2D),but not type 1,protected against amyotrophic lateral sclerosis(ALS).In T2D serum insulin is normal or elevated in the early stages.Type 1 diabetes,characterized by a total lack of insulin,is associated with an increased risk of ALS.The antidiabetic metformin also protects against ALS.Connexin 43(Cx43),an astrocyte protein,operates as an open channel via which toxic substances from astrocytes reach motor neurons to cause ALS.Methods:In the current study we analyzed FDA MedWatch data to determine whether insulin or metformin could reduce the risk of ALS.We performed in silico molecular docking studies and molecular dynamics simulation with Cx43 to determine if insulin or metformin dock within the Cx43 channel and can block it effectively,again reducing risk of ALS.Results:In MedWatch,Insulin use is associated with a significantly reduced risk of ALS(Proportional Reporting Ratio 0.401).Metformin use is associated with a significantly reduced risk of ALS(PRR 0.567).The Human insulin heterodimer docked within center of the Cx43 channel,effectively blocking it.Molecular dynamics simulation showed that the block is highly stable and may be responsible for the protective effect of T2D on ALS.Metformin docks within the Cx43 channel,but the relatively small size of the metformin molecule may not allow it to obstruct the passage of toxic substances from astrocytes to motor neurons.Conclusion:MedWatch data indicate that both insulin and metformin reduce risk of ALS.The results of our in silico docking study and molecular dynamics simulation corroborate our previous findings with Cx31.Insulin docks within the open hemichannel of hexameric Cx43,potentially blocking it.Molecular dynamics simulation showed that the block is stable and may be responsible for the protective effect of T2D and insulin on ALS.
文摘The amyloid hypothesis states that the buildup ofßamyloid in the brain is the main factor for Alzheimer's disease(AD)pathogenesis.An imbalance betweenßamyloid production andß-amyloid clearance causes the advanced stages of the disease,including the development of neurofibrillary tangles containing tau protein.
基金Office of Research Infrastructure of the National Institutes of Health(Grant/Award Number:S10OD018522,S10OD026880)。
文摘In a 2012 study,occasional and low cumulative cannabis use was not associated with adverse effects on pulmonary function.'With tobacco,the more used,the more loss of air flow rate and lung volume.The same was not true with cannabis use.Air flow rate increased rather than decreased with increased exposure to cannabis up to a certain level.
文摘The most prevalent age-related movement condition,Parkinson's disease(PD),is characterized by bradykinesia,resting tremor,unbalanced gait,muscular rigidity,postural instability,as well as some nonmotor symptoms like autonomic and cognitive dysfunctions.
文摘The coronavirus SARS-CoV-2 has already claimed the lives of more than six million people,according to the World Health Organization,and the actual death toll may exceed 18 million.People are avoiding severe cases of COvID-19 thanks to vaccines,medications,and immunity from prior infections.Yet the virus's capacity to block the body's immune response,made possible by its arsenal of proteins,is one factor in its propensity to spread.
