Regulation of α-synuclein expression in down syndrome
The triplication of genes located on chromosome 21 is known to cause a wide spectrum of pathology seen in Down syndrome (DS), including leukemia, seizures, stroke, and mental retardation. Studies on RNA and protein expression of genes in DS brain have demonstrated the role of triplicated genes in se...
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| Published in | Journal of neuroscience research Vol. 90; no. 8; pp. 1589 - 1596 |
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| Format | Journal Article |
| Language | English |
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| Abstract | The triplication of genes located on chromosome 21 is known to cause a wide spectrum of pathology seen in Down syndrome (DS), including leukemia, seizures, stroke, and mental retardation. Studies on RNA and protein expression of genes in DS brain have demonstrated the role of triplicated genes in several DS phenotypes. Significant changes in the expression of nontriplicated genes have also been observed. However, little information is available regarding the role of nonchromosome 21 genes in DS pathology. We have found that α‐synuclein (SNCA), a presynaptic protein whose gene is located on chromosome 6 in the Ts65Dn mouse model for DS, is significantly reduced in the cortex and other brain regions. We hypothesize that this alteration may play a critical role in the reduced synaptic function observed in DS. We have found an increase in the level of neurosin, a key negative regulator of SNCA in Ts65Dn cortex. We have also found increased levels of protein phosphatase 2A, a negative regulator of the activation of tyrosine hydroxylase and a key enzyme in the biosynthetic pathway for dopamine in Ts65Dn cortex. These findings reveal potential target sites for intervention in the treatment of DS pathology. © 2012 Wiley Periodicals, Inc. |
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| AbstractList | The triplication of genes located on chromosome 21 is known to cause a wide spectrum of pathology seen in Down syndrome (DS), including leukemia, seizures, stroke, and mental retardation. Studies on RNA and protein expression of genes in DS brain have demonstrated the role of triplicated genes in several DS phenotypes. Significant changes in the expression of nontriplicated genes have also been observed. However, little information is available regarding the role of nonchromosome 21 genes in DS pathology. We have found that α‐synuclein (SNCA), a presynaptic protein whose gene is located on chromosome 6 in the Ts65Dn mouse model for DS, is significantly reduced in the cortex and other brain regions. We hypothesize that this alteration may play a critical role in the reduced synaptic function observed in DS. We have found an increase in the level of neurosin, a key negative regulator of SNCA in Ts65Dn cortex. We have also found increased levels of protein phosphatase 2A, a negative regulator of the activation of tyrosine hydroxylase and a key enzyme in the biosynthetic pathway for dopamine in Ts65Dn cortex. These findings reveal potential target sites for intervention in the treatment of DS pathology. © 2012 Wiley Periodicals, Inc. The triplication of genes located on chromosome 21 is known to cause a wide spectrum of pathology seen in Down syndrome (DS), including leukemia, seizures, stroke, and mental retardation. Studies on RNA and protein expression of genes in DS brain have demonstrated the role of triplicated genes in several DS phenotypes. Significant changes in the expression of nontriplicated genes have also been observed. However, little information is available regarding the role of nonchromosome 21 genes in DS pathology. We have found that α-synuclein (SNCA), a presynaptic protein whose gene is located on chromosome 6 in the Ts65Dn mouse model for DS, is significantly reduced in the cortex and other brain regions. We hypothesize that this alteration may play a critical role in the reduced synaptic function observed in DS. We have found an increase in the level of neurosin, a key negative regulator of SNCA in Ts65Dn cortex. We have also found increased levels of protein phosphatase 2A, a negative regulator of the activation of tyrosine hydroxylase and a key enzyme in the biosynthetic pathway for dopamine in Ts65Dn cortex. These findings reveal potential target sites for intervention in the treatment of DS pathology. Abstract The triplication of genes located on chromosome 21 is known to cause a wide spectrum of pathology seen in Down syndrome (DS), including leukemia, seizures, stroke, and mental retardation. Studies on RNA and protein expression of genes in DS brain have demonstrated the role of triplicated genes in several DS phenotypes. Significant changes in the expression of nontriplicated genes have also been observed. However, little information is available regarding the role of nonchromosome 21 genes in DS pathology. We have found that α‐synuclein (SNCA), a presynaptic protein whose gene is located on chromosome 6 in the Ts65Dn mouse model for DS, is significantly reduced in the cortex and other brain regions. We hypothesize that this alteration may play a critical role in the reduced synaptic function observed in DS. We have found an increase in the level of neurosin, a key negative regulator of SNCA in Ts65Dn cortex. We have also found increased levels of protein phosphatase 2A, a negative regulator of the activation of tyrosine hydroxylase and a key enzyme in the biosynthetic pathway for dopamine in Ts65Dn cortex. These findings reveal potential target sites for intervention in the treatment of DS pathology. © 2012 Wiley Periodicals, Inc. |
| Author | Patel, Satyam Brown, Ted W. Ramakrishna, Narayan El Idrissi, Abdeslem Meeker, Harry C. |
| Author_xml | – sequence: 1 givenname: Narayan surname: Ramakrishna fullname: Ramakrishna, Narayan email: narayan.ramakrishna@gmail.com organization: Department Molecular Biology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York – sequence: 2 givenname: Harry C. surname: Meeker fullname: Meeker, Harry C. organization: Department of Virology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York – sequence: 3 givenname: Satyam surname: Patel fullname: Patel, Satyam organization: Department Molecular Biology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York – sequence: 4 givenname: Ted W. surname: Brown fullname: Brown, Ted W. organization: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York – sequence: 5 givenname: Abdeslem surname: El Idrissi fullname: El Idrissi, Abdeslem organization: Department of Biology, College of Staten Island, City University of New York, Staten Island, New York |
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| Snippet | The triplication of genes located on chromosome 21 is known to cause a wide spectrum of pathology seen in Down syndrome (DS), including leukemia, seizures,... Abstract The triplication of genes located on chromosome 21 is known to cause a wide spectrum of pathology seen in Down syndrome (DS), including leukemia,... |
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| SubjectTerms | Adolescent Adult Aged alpha-Synuclein - biosynthesis Animals Blotting, Western Brain - metabolism Brain - physiopathology Disease Models, Animal Down Syndrome - metabolism Down Syndrome - physiopathology downregulation Humans Immunohistochemistry Kallikreins - metabolism Mice Middle Aged neurosin Protein Phosphatase 2 - metabolism Reverse Transcriptase Polymerase Chain Reaction Synaptic Transmission - physiology Ts65Dn mouse Young Adult α-synuclein |
| Title | Regulation of α-synuclein expression in down syndrome |
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