In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, n...In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.展开更多
Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and cortex.Patients can present with a variety of symptoms that can broadly be classified into motor symptoms...Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and cortex.Patients can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive decline.The causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.展开更多
Brain-derived neurotrophic factor(BDNF)exerts pleiotropic effects on brain processes including psychiatric disorders,aging,neurodegeneration,and metabolic homeostasis.A simple PubMed search using the key word“BDNF,”...Brain-derived neurotrophic factor(BDNF)exerts pleiotropic effects on brain processes including psychiatric disorders,aging,neurodegeneration,and metabolic homeostasis.A simple PubMed search using the key word“BDNF,”to date,yields over 33,000 publications.From fundamental biology to potential therapeutic applications,BDNF has clearly garnered extensive and significant attention in the field of neurobiology research.展开更多
Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt)...Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, numerous have been the attempts in several preclinical models of Huntington’s disease to evaluate the feasibility of invasive and non-invasive approaches. Thus, the aim of this review is to offer an overview of the most appealing approaches spanning from stem cell-based cell therapy to extracellular vesicles such as exosomes in light of promoting neurogenesis, discussing the results obtained so far, their limits and the future perspectives regarding the neural regeneration in the context of Huntington’s disease.展开更多
Neurotrophic factors,or neurotrophins,are a group of molecules supporting the growth,survival,and differentiation of developing and mature neurons.Given their role in the survival of neurons,and often of specific subs...Neurotrophic factors,or neurotrophins,are a group of molecules supporting the growth,survival,and differentiation of developing and mature neurons.Given their role in the survival of neurons,and often of specific subsets of brain cells,neurotrophins have been implicated in several ways with many neurodegenerative disorders.展开更多
Objective To make early diagnosis of IT15 gene mutation in a Wuhan juvenile-onset Huntington disease （HD） family, for providing them with genetic counseling, and making preparation for the further research on pathog...Objective To make early diagnosis of IT15 gene mutation in a Wuhan juvenile-onset Huntington disease （HD） family, for providing them with genetic counseling, and making preparation for the further research on pathogenesis and experimental therapy of HD. Methods According to the principle of informed consent, we extracted genomic DNA from peripheral blood samples and carried genetic diagnosis of pathogenic exon 1 of IT15 gene by modified touchdown PCR and DNA sequencing methods. Results Eight of twenty-five family members carried abnormal allele： Ⅲ10 Ⅲ12, IIIt4, Ⅳ3, and Ⅴ2 carded （CAG） 48, Ⅳ11 and Ⅳ12 carried （CAG） 67, and Ⅳ14 carried （CAG） 63, in contrast with the 8-25 CAG trinucleotides in the members of control group. Ⅳ14 carried 15 more CAG trinucleotides than her father Ⅲ10. Conclusion The results definitely confirm the diagnosis of HD and indicate the CAG trinucleotide repeat expansion of IT15 gene in this HD family. In addition, CAG expansion results in juvenile-onset and anticipation （characterized by earlier age of onset and increasing severity） of the patientⅣ12.展开更多
文摘In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.
文摘Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and cortex.Patients can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive decline.The causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.
文摘Brain-derived neurotrophic factor(BDNF)exerts pleiotropic effects on brain processes including psychiatric disorders,aging,neurodegeneration,and metabolic homeostasis.A simple PubMed search using the key word“BDNF,”to date,yields over 33,000 publications.From fundamental biology to potential therapeutic applications,BDNF has clearly garnered extensive and significant attention in the field of neurobiology research.
文摘Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, numerous have been the attempts in several preclinical models of Huntington’s disease to evaluate the feasibility of invasive and non-invasive approaches. Thus, the aim of this review is to offer an overview of the most appealing approaches spanning from stem cell-based cell therapy to extracellular vesicles such as exosomes in light of promoting neurogenesis, discussing the results obtained so far, their limits and the future perspectives regarding the neural regeneration in the context of Huntington’s disease.
文摘Neurotrophic factors,or neurotrophins,are a group of molecules supporting the growth,survival,and differentiation of developing and mature neurons.Given their role in the survival of neurons,and often of specific subsets of brain cells,neurotrophins have been implicated in several ways with many neurodegenerative disorders.
文摘Objective To make early diagnosis of IT15 gene mutation in a Wuhan juvenile-onset Huntington disease （HD） family, for providing them with genetic counseling, and making preparation for the further research on pathogenesis and experimental therapy of HD. Methods According to the principle of informed consent, we extracted genomic DNA from peripheral blood samples and carried genetic diagnosis of pathogenic exon 1 of IT15 gene by modified touchdown PCR and DNA sequencing methods. Results Eight of twenty-five family members carried abnormal allele： Ⅲ10 Ⅲ12, IIIt4, Ⅳ3, and Ⅴ2 carded （CAG） 48, Ⅳ11 and Ⅳ12 carried （CAG） 67, and Ⅳ14 carried （CAG） 63, in contrast with the 8-25 CAG trinucleotides in the members of control group. Ⅳ14 carried 15 more CAG trinucleotides than her father Ⅲ10. Conclusion The results definitely confirm the diagnosis of HD and indicate the CAG trinucleotide repeat expansion of IT15 gene in this HD family. In addition, CAG expansion results in juvenile-onset and anticipation （characterized by earlier age of onset and increasing severity） of the patientⅣ12.
