In the central nervous system（CNS）,cyclic adenosine monophosphate（cAMP）plays a critical role in numerous,often concurrent,neuronal functions including survival,growth,differentiation and synaptogenesis.
Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebr...Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.展开更多
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Packaging and storage of glutamate into glutamatergic neuronal vesicles require ATP-dependent vesicular glutamate uptak...Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Packaging and storage of glutamate into glutamatergic neuronal vesicles require ATP-dependent vesicular glutamate uptake systems, which utilize the electrochemical proton gradient as a driving force. Three vesicular glutamate transporters (VGLUT1-3) have been recently identified from neuronal tissue where they play a key role to maintain the vesicular glutamate level. Recently, it has been demonstrated that glutamate signaling is also functional in peripheral neuronal and non-neuronal tissues, and occurs in sites of pituitary, adrenal, pineal glands, bone, GI tract, pancreas,skin, and testis. The glutamate receptors and VGLUTs in digestivesystem have been found in both neuronal and endocrinal cells. The glutamate signaling in the digestive system may have significant relevance to diabetes and GI tract motility disorders. This review will focus on the most recent update of molecular physiology of digestive VGLUTs.展开更多
Accumulating evidence from epidemiological and experi- mental studies indicate that obesity, and its related metabolic consequences of insulin resistance and type 2 diabetes, are associated with accelerated cognitive ...Accumulating evidence from epidemiological and experi- mental studies indicate that obesity, and its related metabolic consequences of insulin resistance and type 2 diabetes, are associated with accelerated cognitive decline （Yates et al., 2012）. The etiology of neurodegeneration in obesity is undoubtedly complex, with vascular, metabolic, inflammatory, and structural changes all likely to play a role （Yates et al., 2012）. The discovery of leptin in 1994 and the subsequent advancement in our understanding that adipose tissue is an endocrine organ that can communicate with the brain to regulate appetite （Zhang et al., 1994） brings about the in- triguing possibility that adipose-brain crosstalk can regulate aspects of neuronal physiology and pathology （Aguilar-Valles et al., 2015）. Indeed neurons have been shown to express receptors for various adipokines, indicating that factors released from adipose tissue have the potential to communi- cate directly with the brain. Research in this area is relatively new, and while epidemiological data points towards the negative consequences of adipose-brain crosstalk （Whitmer et al., 2005）, some intriguing new studies highlight that the secretory profile of adipose tissue might be involved in reduction in neurodegeneration via maintenance of neuronal viability （Tezapsidis et al., 2009; Wan et al., 2015）.展开更多
Rhinovirus(RV)are best known as a common cold virus,but infections with these viruses are also major causes of lower respiratory morbidity in younger children and in children and adults with asthma.Cofactors related t...Rhinovirus(RV)are best known as a common cold virus,but infections with these viruses are also major causes of lower respiratory morbidity in younger children and in children and adults with asthma.Cofactors related to the virus,the host and the environment modify the risk of more severe illness.There are three RV species,and the A and C viruses are most often associated with wheezing illnesses.Host factors that influence the risk of virus-induced wheeze include age,genetics,allergy and asthma and lung function.In addition,the airway microbiome influences the probability of RV wheeze,and RV wheezing illnesses are associated with changes microbial community composition that include increased detection of respiratory pathogens.Interestingly,the host and environmental cofactors that promote wheezing in infancy and in children and adults with asthma are similar.Identification of modifiable host and environmental risk factors for RV wheeze suggests that there are several therapeutic opportunities for prevention and treatment.展开更多
基金supported by National Eye Institute grants R01 EY022129 and EY026766 to MSK and F32 EY025915 to EGC
文摘In the central nervous system（CNS）,cyclic adenosine monophosphate（cAMP）plays a critical role in numerous,often concurrent,neuronal functions including survival,growth,differentiation and synaptogenesis.
文摘Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.
基金Supported by the National Institute of Diabetes and Digestive Kidney Diseases Grant R01-DK063142 and R01-DK33209
文摘Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Packaging and storage of glutamate into glutamatergic neuronal vesicles require ATP-dependent vesicular glutamate uptake systems, which utilize the electrochemical proton gradient as a driving force. Three vesicular glutamate transporters (VGLUT1-3) have been recently identified from neuronal tissue where they play a key role to maintain the vesicular glutamate level. Recently, it has been demonstrated that glutamate signaling is also functional in peripheral neuronal and non-neuronal tissues, and occurs in sites of pituitary, adrenal, pineal glands, bone, GI tract, pancreas,skin, and testis. The glutamate receptors and VGLUTs in digestivesystem have been found in both neuronal and endocrinal cells. The glutamate signaling in the digestive system may have significant relevance to diabetes and GI tract motility disorders. This review will focus on the most recent update of molecular physiology of digestive VGLUTs.
文摘Accumulating evidence from epidemiological and experi- mental studies indicate that obesity, and its related metabolic consequences of insulin resistance and type 2 diabetes, are associated with accelerated cognitive decline （Yates et al., 2012）. The etiology of neurodegeneration in obesity is undoubtedly complex, with vascular, metabolic, inflammatory, and structural changes all likely to play a role （Yates et al., 2012）. The discovery of leptin in 1994 and the subsequent advancement in our understanding that adipose tissue is an endocrine organ that can communicate with the brain to regulate appetite （Zhang et al., 1994） brings about the in- triguing possibility that adipose-brain crosstalk can regulate aspects of neuronal physiology and pathology （Aguilar-Valles et al., 2015）. Indeed neurons have been shown to express receptors for various adipokines, indicating that factors released from adipose tissue have the potential to communi- cate directly with the brain. Research in this area is relatively new, and while epidemiological data points towards the negative consequences of adipose-brain crosstalk （Whitmer et al., 2005）, some intriguing new studies highlight that the secretory profile of adipose tissue might be involved in reduction in neurodegeneration via maintenance of neuronal viability （Tezapsidis et al., 2009; Wan et al., 2015）.
文摘Rhinovirus(RV)are best known as a common cold virus,but infections with these viruses are also major causes of lower respiratory morbidity in younger children and in children and adults with asthma.Cofactors related to the virus,the host and the environment modify the risk of more severe illness.There are three RV species,and the A and C viruses are most often associated with wheezing illnesses.Host factors that influence the risk of virus-induced wheeze include age,genetics,allergy and asthma and lung function.In addition,the airway microbiome influences the probability of RV wheeze,and RV wheezing illnesses are associated with changes microbial community composition that include increased detection of respiratory pathogens.Interestingly,the host and environmental cofactors that promote wheezing in infancy and in children and adults with asthma are similar.Identification of modifiable host and environmental risk factors for RV wheeze suggests that there are several therapeutic opportunities for prevention and treatment.
