The dopaminergic system controls several vital central nervous system functions,including the control of movement,reward behaviors and cognition.Alterations of dopaminergic signaling are involved in the pathogenesis o...The dopaminergic system controls several vital central nervous system functions,including the control of movement,reward behaviors and cognition.Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders,in particular Parkinson’s disease,which are associated with a subtle and chronic inflammatory response.A substantial body of evidence has demonstrated the non-neuronal expression of dopamine,its receptors and of the machinery that governs synthesis,secretion and storage of dopamine across several immune cell types.This review aims to summarize current knowledge on the role and expression of dopamine in immune cells.One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine,in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease.A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation.These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.展开更多
Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-...Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-repair ability of neuronal cells, which undergo progressive deterioration. Once initiated, this process hampers the already limited regenerative power of the central nervous system, making the search for new therapeutic strategies particularly difficult in elderly affected patients. So far, mesenchymal stem cells have proven to be a viable option to ameliorate certain aspects of neurodegeneration, as they possess high proliferative rate and differentiate in vitro into multiple lineages. However, accumulating data have demonstrated that during longterm culture, mesenchymal stem cells undergo spontaneous transformation. Transformed mesenchymal stem cells show typical features of senescence, including the progressive shortening of telomers, which results in cell loss and, as a consequence, hampered regenerative potential. These evidences, in line with those observed in mesenchymal stem cells isolated from old donors, suggest that senescence may represent a limit to mesenchymal stem cells exploitation in therapy, prompting scholars to either find alternative sources of pluripotent cells or to arrest the age-re- lated transformation. In the present review, we summarize findings from recent literature, and critically discuss some of the major hurdles encountered in the search of appropriate sources of mesenchymal stem cells, as well as benefits arising from their use in neurodegenerative diseases. Finally, we provide some insights that may aid in the development of strategies to arrest or, at least, delay the aging of mesenchymal stem cells to improve their therapeutic potential.展开更多
Evidence suggests that rapid changes to supporting glia may predispose individuals with spinal cord injury(SCI) to such comorbidities. Here, we interrogated the expression of astrocyte-and microglial-specific markers ...Evidence suggests that rapid changes to supporting glia may predispose individuals with spinal cord injury(SCI) to such comorbidities. Here, we interrogated the expression of astrocyte-and microglial-specific markers glial fibrillary acidic protein(GFAP) and ionized calcium binding adaptor molecule 1(Iba1) in the rat brain in the first 24 hours following SCI. Female Sprague-Dawley rats underwent thoracic laminectomy;half of the rats received a mild contusion injury at the level of the T10 vertebral body(SCI group), the other half did not(Sham group). Twenty-four hours post-surgery the amygdala, periaqueductal grey, prefrontal cortex, hypothalamus, lateral thalamus, hippocampus(dorsal and ventral) in rats were collected. GFAP and Iba1 m RNA and protein levels were measured by real-time quantitative polymerase chain reaction and Western blot. In SCI rats, GFAP m RNA and protein expression increased in the amygdala and hypothalamus. In contrast, gene and protein expression decreased in the thalamus and dorsal hippocampus. Interestingly, Iba1 transcripts and proteins were significantly diminished only in the dorsal and ventral hippocampus, where gene expression diminished. These findings demonstrate that as early as 24 hours post-SCI there are region-specific disruptions of GFAP and Iba1 transcript and protein levels in higher brain regions. All procedures were approved by the University of Technology Sydney Institutional Animal Care and Ethics Committee(UTS ACEC13-0069).展开更多
Dipeptidyl peptidase IV(DPP-IV)is a serine protease best known for its role in inactivating glucagon-like peptide-1(GLP-1),pituitary adenylate cyclase-activating polypeptide(PACAP)and glucose-dependent insulinotropic ...Dipeptidyl peptidase IV(DPP-IV)is a serine protease best known for its role in inactivating glucagon-like peptide-1(GLP-1),pituitary adenylate cyclase-activating polypeptide(PACAP)and glucose-dependent insulinotropic peptide(GIP),three stimulators of pancreatic insulin secretion with beneficial effects on glucose disposal.Owing to the relationship between DPP-IV and these peptides,inhibition of DPP-IV enzyme activity is considered as an attractive treatment option for diabetic patients.Nonetheless,increasing studies support the idea that DPP-IV might also be involved in the development of neurological disorders with a neuroinflammatory component,potentially through its non-incretin activities on immune cells.In this review article,we aim at highlighting recent literature describing the therapeutic value of DPP-IV inhibitors for the treatment of such neurological conditions.Finally,we will illustrate some of the promising results obtained using berberine,a plant extract with potent inhibitory activity on DPP-IV.展开更多
Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatica...Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatically （about 30%） in people aged 80 years or older （Selkoe, 2002）. Nowadays, considering the increasing mean lifespan of populations in developed countries, the disease is becoming more and more a health concern, and the search for an effective cure has turned into＂a real need＂.展开更多
基金supported by a Research Development Fund(UTS Start-Up Grant 2018)from the University of Technology Sydney to AC。
文摘The dopaminergic system controls several vital central nervous system functions,including the control of movement,reward behaviors and cognition.Alterations of dopaminergic signaling are involved in the pathogenesis of neurodegenerative and psychiatric disorders,in particular Parkinson’s disease,which are associated with a subtle and chronic inflammatory response.A substantial body of evidence has demonstrated the non-neuronal expression of dopamine,its receptors and of the machinery that governs synthesis,secretion and storage of dopamine across several immune cell types.This review aims to summarize current knowledge on the role and expression of dopamine in immune cells.One of the goals is to decipher the complex mechanisms through which these cell types respond to dopamine,in order to address the impact this has on neurodegenerative and psychiatric pathologies such as Parkinson’s disease.A further aim is to illustrate the gaps in our understanding of the physiological roles of dopamine to encourage more targeted research focused on understanding the consequences of aberrant dopamine production on immune regulation.These highlights may prompt scientists in the field to consider alternative functions of this important neurotransmitter when targeting neuroinflammatory/neurodegenerative pathologies.
基金part supported by the Department of Biomedical Sciences and Biotechnologies,Medical School,University of Catania,Italy(National Grant.PON 01_00110)
文摘Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-repair ability of neuronal cells, which undergo progressive deterioration. Once initiated, this process hampers the already limited regenerative power of the central nervous system, making the search for new therapeutic strategies particularly difficult in elderly affected patients. So far, mesenchymal stem cells have proven to be a viable option to ameliorate certain aspects of neurodegeneration, as they possess high proliferative rate and differentiate in vitro into multiple lineages. However, accumulating data have demonstrated that during longterm culture, mesenchymal stem cells undergo spontaneous transformation. Transformed mesenchymal stem cells show typical features of senescence, including the progressive shortening of telomers, which results in cell loss and, as a consequence, hampered regenerative potential. These evidences, in line with those observed in mesenchymal stem cells isolated from old donors, suggest that senescence may represent a limit to mesenchymal stem cells exploitation in therapy, prompting scholars to either find alternative sources of pluripotent cells or to arrest the age-re- lated transformation. In the present review, we summarize findings from recent literature, and critically discuss some of the major hurdles encountered in the search of appropriate sources of mesenchymal stem cells, as well as benefits arising from their use in neurodegenerative diseases. Finally, we provide some insights that may aid in the development of strategies to arrest or, at least, delay the aging of mesenchymal stem cells to improve their therapeutic potential.
基金The University of Technology Sydney(UTS)Start-up Research Grant 2018 funded this study(to AC)。
文摘Evidence suggests that rapid changes to supporting glia may predispose individuals with spinal cord injury(SCI) to such comorbidities. Here, we interrogated the expression of astrocyte-and microglial-specific markers glial fibrillary acidic protein(GFAP) and ionized calcium binding adaptor molecule 1(Iba1) in the rat brain in the first 24 hours following SCI. Female Sprague-Dawley rats underwent thoracic laminectomy;half of the rats received a mild contusion injury at the level of the T10 vertebral body(SCI group), the other half did not(Sham group). Twenty-four hours post-surgery the amygdala, periaqueductal grey, prefrontal cortex, hypothalamus, lateral thalamus, hippocampus(dorsal and ventral) in rats were collected. GFAP and Iba1 m RNA and protein levels were measured by real-time quantitative polymerase chain reaction and Western blot. In SCI rats, GFAP m RNA and protein expression increased in the amygdala and hypothalamus. In contrast, gene and protein expression decreased in the thalamus and dorsal hippocampus. Interestingly, Iba1 transcripts and proteins were significantly diminished only in the dorsal and ventral hippocampus, where gene expression diminished. These findings demonstrate that as early as 24 hours post-SCI there are region-specific disruptions of GFAP and Iba1 transcript and protein levels in higher brain regions. All procedures were approved by the University of Technology Sydney Institutional Animal Care and Ethics Committee(UTS ACEC13-0069).
文摘Dipeptidyl peptidase IV(DPP-IV)is a serine protease best known for its role in inactivating glucagon-like peptide-1(GLP-1),pituitary adenylate cyclase-activating polypeptide(PACAP)and glucose-dependent insulinotropic peptide(GIP),three stimulators of pancreatic insulin secretion with beneficial effects on glucose disposal.Owing to the relationship between DPP-IV and these peptides,inhibition of DPP-IV enzyme activity is considered as an attractive treatment option for diabetic patients.Nonetheless,increasing studies support the idea that DPP-IV might also be involved in the development of neurological disorders with a neuroinflammatory component,potentially through its non-incretin activities on immune cells.In this review article,we aim at highlighting recent literature describing the therapeutic value of DPP-IV inhibitors for the treatment of such neurological conditions.Finally,we will illustrate some of the promising results obtained using berberine,a plant extract with potent inhibitory activity on DPP-IV.
文摘Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatically （about 30%） in people aged 80 years or older （Selkoe, 2002）. Nowadays, considering the increasing mean lifespan of populations in developed countries, the disease is becoming more and more a health concern, and the search for an effective cure has turned into＂a real need＂.
