title: Regulation of α-synuclein expression in Down syndrome.
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.
authors.affiliation: Department Molecular Biology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA. narayan.ramakrishna@gmail.com
authors.forename: Narayan
authors.initials: N
authors.lastname: Ramakrishna
authors.forename: Harry C
authors.initials: HC
authors.lastname: Meeker
authors.forename: Satyam
authors.initials: S
authors.lastname: Patel
authors.forename: Ted W
authors.initials: TW
authors.lastname: Brown
authors.forename: Abdeslem
authors.initials: A
authors.lastname: El Idrissi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D054648:Protein Phosphatase 2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009435:Synaptic Transmission / Q000502:physiology*; D055815:Young Adult; D051844:alpha-Synuclein / Q000096:biosynthesis*
chemical_list: D051844:alpha-Synuclein; D054648:Protein Phosphatase 2; D007610:Kallikreins; C491223:Prss18 protein, mouse