TORSIN A AND THE PATHOPHYSIOLOGY OF DYSTONIA Mutations of the DYT1 gene cause early onset torsion dystonia. This gene encodes torsinA, a member of a novel family of proteins with homology to the HSP 100/CLP family of heat shock proteins. In preliminary studies, we have found that the gene for torsin A is active in nerve cells in several regions of normal adult human brain, including the dopamine neurons of the substantia nigra pars compacta. We have also found that the gene is always active in the brains of patients who are ill for more than a day but not in the brains of those who die suddenly. This finding is consistent with, but does not prove, that torsinA is a stress response protein. In this application we seek funding to obtain detailed information about the localization and regulation of the torsinA mRNA and protein in both human brain and genetically engineered rodent models. We will determine exactly which cells in human and mouse brain contain the mRNA and protein, where in the cells the protein is located, whether mRNA expression is regulated by stress and whether the mutation effects the location or amount of mRNA expression, the subcellular location of the protein or the function of dopamine neurons. These data are essential to the construction of mechanistic models of the neural dysfunction which produces dystonia.
| Waugh, Jeff L; Kuster, John K; Levenstein, Jacob M et al. (2016) Thalamic Volume Is Reduced in Cervical and Laryngeal Dystonias. PLoS One 11:e0155302 |
| Sundermann, Erin Elizabeth; Wang, Cuiling; Katz, Mindy et al. (2016) Cholesteryl ester transfer protein genotype modifies the effect of apolipoprotein ?4 on memory decline in older adults. Neurobiol Aging 41:200.e7-200.e12 |
| DeAndrade, Mark P; Trongnetrpunya, Amy; Yokoi, Fumiaki et al. (2016) Electromyographic evidence in support of a knock-in mouse model of DYT1 Dystonia. Mov Disord 31:1633-1639 |
| de Carvalho Aguiar, Patricia; Borges, Vanderci; Ferraz, Henrique Ballalai et al. (2015) Novel compound heterozygous mutations in PRKRA cause pure dystonia. Mov Disord 30:877-8 |
| Alcalay, Roy N; Mejia-Santana, Helen; Mirelman, Anat et al. (2015) Neuropsychological performance in LRRK2 G2019S carriers with Parkinson's disease. Parkinsonism Relat Disord 21:106-10 |
| Saunders-Pullman, Rachel; Alcalay, Roy N; Mirelman, Anat et al. (2015) REM sleep behavior disorder, as assessed by questionnaire, in G2019S LRRK2 mutation PD and carriers. Mov Disord 30:1834-9 |
| Gupte, Manisha; Alcalay, Roy N; Mejia-Santana, Helen et al. (2015) Interest in genetic testing in Ashkenazi Jewish Parkinson's disease patients and their unaffected relatives. J Genet Couns 24:238-46 |
| Mirelman, Anat; Alcalay, Roy N; Saunders-Pullman, Rachel et al. (2015) Nonmotor symptoms in healthy Ashkenazi Jewish carriers of the G2019S mutation in the LRRK2 gene. Mov Disord 30:981-6 |
| Yokoi, Fumiaki; Dang, Mai T; Liu, Jun et al. (2015) Decreased dopamine receptor 1 activity and impaired motor-skill transfer in Dyt1 ?GAG heterozygous knock-in mice. Behav Brain Res 279:202-10 |
| Yokoi, Fumiaki; Chen, Huan-Xin; Dang, Mai Tu et al. (2015) Behavioral and electrophysiological characterization of Dyt1 heterozygous knockout mice. PLoS One 10:e0120916 |
Showing the most recent 10 out of 82 publications
