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
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
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
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
Developmental motifs in neurodegeneration:Neurodegeneration,the prominent feature of neurodegenerative disease,is characterized by the progressive and selective loss of neuronal function.As some of the pathologies cau...Developmental motifs in neurodegeneration:Neurodegeneration,the prominent feature of neurodegenerative disease,is characterized by the progressive and selective loss of neuronal function.As some of the pathologies caused by neurodegeneration may be irreversible,early intervention will be required for the treatments that aim to slow or halt the manifestation of these diseases.Traditionally,neurodegeneration evokes the idea of a progressive decline of brain function.展开更多
Huntington’s disease (HD)(OMIM 143100) is an autosomal dominant neurodegenerative disorder caused by a monogenic mutation in the huntingtin gene (HTT),which induces typical midlife onset and age-dependent progression...Huntington’s disease (HD)(OMIM 143100) is an autosomal dominant neurodegenerative disorder caused by a monogenic mutation in the huntingtin gene (HTT),which induces typical midlife onset and age-dependent progression with major symptoms including choreic movements,psychiatric disorders,and cognitive impairment(Gusella et al.,2021).After the 1993 discovery of a pathogenic expansion of the CAG trinucleotide repeat beyond 35 in HTT exon 1 as a causative factor for HD,many animal,mammalian cell and yeast models expressing mutant HTT (mHtt) with abnormal CAG repeats have been created to study CAG repeat-induced toxicity (Naphade et al.,2019;Gusella et al.,2021).展开更多
The renin-angiotensin system(RAS)was originally conceived as a circulating hormonal system involved in the regulation of cardiovascular and renal homeostasis.With the discovery of local RAS components in diverse organ...The renin-angiotensin system(RAS)was originally conceived as a circulating hormonal system involved in the regulation of cardiovascular and renal homeostasis.With the discovery of local RAS components in diverse organs,including the brain,and related biologically active peptides.展开更多
Huntington’s disease is a genetic disease caused by expanded CAG repeats on exon 1 of the huntingtin gene located on chromosome 4.Compelling evidence implicates impaired mitochondrial energetics,altered mitochondrial...Huntington’s disease is a genetic disease caused by expanded CAG repeats on exon 1 of the huntingtin gene located on chromosome 4.Compelling evidence implicates impaired mitochondrial energetics,altered mitochondrial biogenesis and quality control,disturbed mitochondrial trafficking,oxidative stress and mitochondrial calcium dyshomeostasis in the pathogenesis of the disorder.Unfortunately,conventional mitochondrial-targeted molecules,such as cysteamine,creatine,coenzyme Q10,or triheptanoin,yielded negative or inconclusive results.However,future therapeutic strategies,aiming to restore mitochondrial biogenesis,improving the fission/fusion balance,and improving mitochondrial trafficking,could prove useful tools in improving the phenotype of Huntington’s disease and,used in combination with genome-editing methods,could lead to a cure for the disease.展开更多
On February 16,a new study published in the journal of Nature Biomedical Engineering demonstrated the potential of CRISPR/Cas9 technology to combat Huntington’s disease(HD),a devastating neurodegenerative disorder.
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Developmental motifs in neurodegeneration:Neurodegeneration,the prominent feature of neurodegenerative disease,is characterized by the progressive and selective loss of neuronal function.As some of the pathologies caused by neurodegeneration may be irreversible,early intervention will be required for the treatments that aim to slow or halt the manifestation of these diseases.Traditionally,neurodegeneration evokes the idea of a progressive decline of brain function.
基金National Institute of General Medical Sciences grant (SC1GM1111178)to JX。
文摘Huntington’s disease (HD)(OMIM 143100) is an autosomal dominant neurodegenerative disorder caused by a monogenic mutation in the huntingtin gene (HTT),which induces typical midlife onset and age-dependent progression with major symptoms including choreic movements,psychiatric disorders,and cognitive impairment(Gusella et al.,2021).After the 1993 discovery of a pathogenic expansion of the CAG trinucleotide repeat beyond 35 in HTT exon 1 as a causative factor for HD,many animal,mammalian cell and yeast models expressing mutant HTT (mHtt) with abnormal CAG repeats have been created to study CAG repeat-induced toxicity (Naphade et al.,2019;Gusella et al.,2021).
基金financial support from the Brazili an government funding agencies:FAPEMIG(Funda??o de AmparoàPesquisa do Estado de Minas Gerais,Brazil)CNPq(Conselho Nacional de Desenvoivimento Cientificoe Tecnologico,Brazil)+1 种基金CAPES(Coordena??o de Aperfei?oamento de Pessoal de Nivel Superior)ALT received financial support from UTHealth Department of Psychiatry and Behavioral Sciences,NIH/NIA,TARCC.ASM and ALT are CNPq fellowship recipients。
文摘The renin-angiotensin system(RAS)was originally conceived as a circulating hormonal system involved in the regulation of cardiovascular and renal homeostasis.With the discovery of local RAS components in diverse organs,including the brain,and related biologically active peptides.
文摘Huntington’s disease is a genetic disease caused by expanded CAG repeats on exon 1 of the huntingtin gene located on chromosome 4.Compelling evidence implicates impaired mitochondrial energetics,altered mitochondrial biogenesis and quality control,disturbed mitochondrial trafficking,oxidative stress and mitochondrial calcium dyshomeostasis in the pathogenesis of the disorder.Unfortunately,conventional mitochondrial-targeted molecules,such as cysteamine,creatine,coenzyme Q10,or triheptanoin,yielded negative or inconclusive results.However,future therapeutic strategies,aiming to restore mitochondrial biogenesis,improving the fission/fusion balance,and improving mitochondrial trafficking,could prove useful tools in improving the phenotype of Huntington’s disease and,used in combination with genome-editing methods,could lead to a cure for the disease.
文摘On February 16,a new study published in the journal of Nature Biomedical Engineering demonstrated the potential of CRISPR/Cas9 technology to combat Huntington’s disease(HD),a devastating neurodegenerative disorder.
