Experimental RNA interference (RNAi) leading to the selective knockdown of gene function is induced by introducing into cells either double stranded RNA (dsRNA), or short interfering RNA (siRNA) fragments into which d...Experimental RNA interference (RNAi) leading to the selective knockdown of gene function is induced by introducing into cells either double stranded RNA (dsRNA), or short interfering RNA (siRNA) fragments into which dsRNA is cut. The siRNA triggers degradation of homologous messengerRNA (mRNA). Widely used as a research tool in the genetic model organisms Caenorhabditis elegans, Drosophila melanogaster and mouse to investigate the function of individual genes, RNAi has also been deployed in genome-wide, specific gene-knockdown screens. Recent rapid progress in the application of RNAi to mammalian cells, including neurons and muscle cells, offers new approaches to drug target identification and validation.Advances in targeted delivery of RNAi-inducing molecules have raised the possibility of using RNAi directly as a therapy for a variety of human genetic and other neural and neuromuscular disorders. Here, we review examples of the application of RNAi to worm, fly and mouse models of such diseases aimed at understanding their pathophysiology.展开更多
Since the sequencing of the human genome was announced in 2001, researchers have an increased ability to discern the genetic basis for diseases. This reference genome has opened the door to translational medicine whic...Since the sequencing of the human genome was announced in 2001, researchers have an increased ability to discern the genetic basis for diseases. This reference genome has opened the door to translational medicine which may be defined as the use of data acquisition and analysis to improve medical care, including prognostics, diagnostics, preventive intervention, therapeutic selection, and individualized treatment based on the complex interaction between inherited and acquired elements of human variation. It is an approach that will build on the comprehensive nature of the genome sciences. It aims at detecting and understanding of all genetic variations of the human genome that contribute to the manifestation and progression of disease.It is clear that what is really new in genomic medicine is the application of genomic technology on a large scale to virtually every problem of medicine. Genomic medicine goes well beyond the traditional boundaries of genetics in medicine. As a clinical paradigm, translational medicine provided global, comprehensive, and multidimensional treatment and management strategies based on the science emerging from the study of genomics and genetics of human diseases. Translational medicine will have a transformative role in healthcare, whose emphasis can be anticipated to dramatically shift from disease treatment to health maintenance.展开更多
Charcot-Marie-Tooth disease (CMT) affects the peripheral nervous system. It is generally inherited in an autosomal dominant pattern, but also is inherited in recessive or an X-linked pattern. The degree of severity ca...Charcot-Marie-Tooth disease (CMT) affects the peripheral nervous system. It is generally inherited in an autosomal dominant pattern, but also is inherited in recessive or an X-linked pattern. The degree of severity can vary greatly from patient to patient, even within the same family. Traditionally, the different classes of CMT have been divided into demyelinating forms and axonal forms. Until 10 years ago, the genetic basis of CMT disease was largely unknown. An intrachromosomal duplication on chromosome 17 was found in 1991, and a point mutation in the peripheral myelin protein-22 gene was discovered in 1992. The work starts a new stage of the molecular basis of this large group of peripheral neuropathies. In this review, we will summarize what is known today about the genetics of CMT, and what we have learned about the underlying disease mechanisms.展开更多
Objective:To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA). Methods:The cells from human fetal cerebellum (8-10 weeks of gestation) were grown and ...Objective:To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA). Methods:The cells from human fetal cerebellum (8-10 weeks of gestation) were grown and expanded in vitro. The cultured neurospheres were then implanted into the dentate nuclei of patients by stereo tactic operation. Totally,12 patients (7 males and 5 females with age ranging 22-62 years,mean 43 years) were treated by this operation from August 2006 to August 2008. Results:The cells of fetal cerebellum were expanded by 107 folds in undifferentiated state in the culture. After the operation,no rejection was detected. Follow up,the effective rates were 58.3% after 3 months,75.0% after 6 months,and 66.7% for 12-24 months (mean 18 months). Conclusion:the transplantation of in vitro cultured neural stem cell is a feasible and effective treatment for inherited CA,but the long term effectiveness need to be taken in consideration.展开更多
Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 differe...Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 different human diseases, which superficially seem to share little with one another, result from LMNA mutations. The position of the mutation within LMNA appears to be associated with the phenotypes. This review gives an overview of genotype-phenotype relationship and describes recent advances in animal models and pathogenic mechanisms.展开更多
文摘Experimental RNA interference (RNAi) leading to the selective knockdown of gene function is induced by introducing into cells either double stranded RNA (dsRNA), or short interfering RNA (siRNA) fragments into which dsRNA is cut. The siRNA triggers degradation of homologous messengerRNA (mRNA). Widely used as a research tool in the genetic model organisms Caenorhabditis elegans, Drosophila melanogaster and mouse to investigate the function of individual genes, RNAi has also been deployed in genome-wide, specific gene-knockdown screens. Recent rapid progress in the application of RNAi to mammalian cells, including neurons and muscle cells, offers new approaches to drug target identification and validation.Advances in targeted delivery of RNAi-inducing molecules have raised the possibility of using RNAi directly as a therapy for a variety of human genetic and other neural and neuromuscular disorders. Here, we review examples of the application of RNAi to worm, fly and mouse models of such diseases aimed at understanding their pathophysiology.
文摘Since the sequencing of the human genome was announced in 2001, researchers have an increased ability to discern the genetic basis for diseases. This reference genome has opened the door to translational medicine which may be defined as the use of data acquisition and analysis to improve medical care, including prognostics, diagnostics, preventive intervention, therapeutic selection, and individualized treatment based on the complex interaction between inherited and acquired elements of human variation. It is an approach that will build on the comprehensive nature of the genome sciences. It aims at detecting and understanding of all genetic variations of the human genome that contribute to the manifestation and progression of disease.It is clear that what is really new in genomic medicine is the application of genomic technology on a large scale to virtually every problem of medicine. Genomic medicine goes well beyond the traditional boundaries of genetics in medicine. As a clinical paradigm, translational medicine provided global, comprehensive, and multidimensional treatment and management strategies based on the science emerging from the study of genomics and genetics of human diseases. Translational medicine will have a transformative role in healthcare, whose emphasis can be anticipated to dramatically shift from disease treatment to health maintenance.
文摘Charcot-Marie-Tooth disease (CMT) affects the peripheral nervous system. It is generally inherited in an autosomal dominant pattern, but also is inherited in recessive or an X-linked pattern. The degree of severity can vary greatly from patient to patient, even within the same family. Traditionally, the different classes of CMT have been divided into demyelinating forms and axonal forms. Until 10 years ago, the genetic basis of CMT disease was largely unknown. An intrachromosomal duplication on chromosome 17 was found in 1991, and a point mutation in the peripheral myelin protein-22 gene was discovered in 1992. The work starts a new stage of the molecular basis of this large group of peripheral neuropathies. In this review, we will summarize what is known today about the genetics of CMT, and what we have learned about the underlying disease mechanisms.
文摘Objective:To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA). Methods:The cells from human fetal cerebellum (8-10 weeks of gestation) were grown and expanded in vitro. The cultured neurospheres were then implanted into the dentate nuclei of patients by stereo tactic operation. Totally,12 patients (7 males and 5 females with age ranging 22-62 years,mean 43 years) were treated by this operation from August 2006 to August 2008. Results:The cells of fetal cerebellum were expanded by 107 folds in undifferentiated state in the culture. After the operation,no rejection was detected. Follow up,the effective rates were 58.3% after 3 months,75.0% after 6 months,and 66.7% for 12-24 months (mean 18 months). Conclusion:the transplantation of in vitro cultured neural stem cell is a feasible and effective treatment for inherited CA,but the long term effectiveness need to be taken in consideration.
文摘Laminopathies are genetic diseases that encompass a wide spectrum of phenotypes with diverse tissue pathologies and result mainly from mutations in the LMNA gene encoding nuclear lamin A/C. To date, at least 9 different human diseases, which superficially seem to share little with one another, result from LMNA mutations. The position of the mutation within LMNA appears to be associated with the phenotypes. This review gives an overview of genotype-phenotype relationship and describes recent advances in animal models and pathogenic mechanisms.
