With the efforts in developmental biology and neuroscience during the past several decades,our knowledge has been significantly advanced about the genetic,cellular,and molecular mechanisms underlying brain development...With the efforts in developmental biology and neuroscience during the past several decades,our knowledge has been significantly advanced about the genetic,cellular,and molecular mechanisms underlying brain development and function.However,we should keep in mind that the human brain is the product of complex evolutionary processes,and there is a trade-off between brain evolution and neurological disorders[1].展开更多
The development of spinal cord is a precisely and sequentially regulated process, which is controlled bysignaling pathways and transcription factors in each stage. Overwhelming data have shown the essential roles of B...The development of spinal cord is a precisely and sequentially regulated process, which is controlled bysignaling pathways and transcription factors in each stage. Overwhelming data have shown the essential roles of BMP signaling in different stages of this developmental process. It is also clear that the proper functions of BMP signaling require its cross-talk with several other signaling pathways including Notch, Wnt and retinoic acid (RA) pathways. Here, we highlight the recent advancement in understanding the roles of BMP signaling during neurogenesis, neural tube patterning, axon development and glial differentiation in the spinal cord, and emphasize its integrations with other pathways during these processes.展开更多
Alzheimer’s disease(AD)is characterized by progressive synaptic dysfunction,neuronal death,and brain atrophy,with amyloid-p(Ap)plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the br...Alzheimer’s disease(AD)is characterized by progressive synaptic dysfunction,neuronal death,and brain atrophy,with amyloid-p(Ap)plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue,which all lead to loss of cognitive function.Pathogenic mutations in the well-known AD causal genes including APP,PSEN1,and PSEN2 impair a variety of pathways,including protein processing,axonal transport,and metabolic homeostasis.Here we identified a missense variant rs117916664(c.896T>C,p.Asn299Ser[p.N299S])of the acetyl-CoA acyltransferase 1(ACM1)gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort.Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity,impairing lysosomal function,and aggravating the Ap pathology and neuronal loss,which finally caused cognitive impairment in a murine model.Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis.展开更多
Dear Editor,Peripheral neuropathy is a group of devastating diseases affecting periphe-ral nerves and may cause symptoms such as extreme numbness,muscle weakness,and paralysis.Currently,there are no effective therapie...Dear Editor,Peripheral neuropathy is a group of devastating diseases affecting periphe-ral nerves and may cause symptoms such as extreme numbness,muscle weakness,and paralysis.Currently,there are no effective therapies for these diseases.Great progress has been made in identifying genetic causes for peripheral neuropathy owing to the advances in genetic testing in the last decade.For example,>100 genes have been identified to be associated with Charcot–Marie–Tooth(CMT)neuropathy,a group of disorders among the most common forms of inherited peripheral neuropathy.展开更多
基金supported by the Science and Technology Department of Yunnan Province(202305AH340007)the National Natural Science Foundation of China(32371017)the National Key Research and Development Program of China(2023YFA1800500).
文摘With the efforts in developmental biology and neuroscience during the past several decades,our knowledge has been significantly advanced about the genetic,cellular,and molecular mechanisms underlying brain development and function.However,we should keep in mind that the human brain is the product of complex evolutionary processes,and there is a trade-off between brain evolution and neurological disorders[1].
文摘The development of spinal cord is a precisely and sequentially regulated process, which is controlled bysignaling pathways and transcription factors in each stage. Overwhelming data have shown the essential roles of BMP signaling in different stages of this developmental process. It is also clear that the proper functions of BMP signaling require its cross-talk with several other signaling pathways including Notch, Wnt and retinoic acid (RA) pathways. Here, we highlight the recent advancement in understanding the roles of BMP signaling during neurogenesis, neural tube patterning, axon development and glial differentiation in the spinal cord, and emphasize its integrations with other pathways during these processes.
基金The study was supported by the National Natural Science Foundation of China(31730037 to Y.-G.Y.,31900737 to R.L.,82022017 to D.-F.Z.)the Strategic Priority Research Program(B)of CAS(XDB02020003 to Y.-G.Y.)+5 种基金the Bureau of Frontier Sciences and Education,CAS(grant no.QYZDJ-SSW-SMC005 to Y.-G.Y.)the Original Innovation Project"from 0 to 1"of Basic Frontier Scientific Research Program,CAS(ZDBS-LY-SM031 to R.L.)the Yunnan Science and Technology Plan Project(202001AT070107 to R.L)the CAS"Light of West China"Program(2020000023 to R.L.)the Youth Innovation Promotion Association of CAS(to R.L.and D.-F.Z.)the Training of High-Level Health Technical Personnel in Yunnan Province,Medical Academic Leader(D-2018047 to H.-Y.J.).
文摘Alzheimer’s disease(AD)is characterized by progressive synaptic dysfunction,neuronal death,and brain atrophy,with amyloid-p(Ap)plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue,which all lead to loss of cognitive function.Pathogenic mutations in the well-known AD causal genes including APP,PSEN1,and PSEN2 impair a variety of pathways,including protein processing,axonal transport,and metabolic homeostasis.Here we identified a missense variant rs117916664(c.896T>C,p.Asn299Ser[p.N299S])of the acetyl-CoA acyltransferase 1(ACM1)gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort.Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity,impairing lysosomal function,and aggravating the Ap pathology and neuronal loss,which finally caused cognitive impairment in a murine model.Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis.
基金supported by grants from the STI2030-Major Projects(2021ZD0202501)the National Natural Science Foundation of China(NSFC)(82150003,91949104,and 31871022)+1 种基金Zhejiang Province NSFC(LY19H090135),the National Institutes of Health(NIH)(R35 GM139627)Open Project from the State Key Laboratory of Genetic Resources and Evolution of China(GREKF20-08).
文摘Dear Editor,Peripheral neuropathy is a group of devastating diseases affecting periphe-ral nerves and may cause symptoms such as extreme numbness,muscle weakness,and paralysis.Currently,there are no effective therapies for these diseases.Great progress has been made in identifying genetic causes for peripheral neuropathy owing to the advances in genetic testing in the last decade.For example,>100 genes have been identified to be associated with Charcot–Marie–Tooth(CMT)neuropathy,a group of disorders among the most common forms of inherited peripheral neuropathy.