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Rhes Suppression Enhances Disease Phenotypes in Huntington's

Cell culture studies suggest that a striatal-enriched protein, Rhes, may account for this vulnerability. ... had increased anxiety-like behaviors and enhanced striatal atrophy as measured by longitudinal MRI when compared to control treated mice. These findings raise ... toxic role of Rhes in causing striatal neuronal loss and.


Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and

Aug 19, 2015 ... Rasd2 (Rhes) is a GTP-binding protein (Falk et al, 1999) highly enriched in the striatum and nucleus accumbens of rodents and developmentally regulated by thyroid hormone activity (Vallortigara et al, 2008, 2009; Vargiu et al, 2001) and by dopamine (DA) innervation in adult rats (Harrison and LaHoste ...


Rhes, a striatal–enriched small G–protein, mediates mTOR

small G–protein, accounts for the unique neuropathology of Huntington's Disease (HD) by enhancing ... F.E conducted the L–DOPA and behavioral experiments, under the direction of A.U. R.B generated the Rhes constructs. S.K .... primarily via the dopamine system, Rhes deleted mice would be predicted to manifest.


Rhes Is Involved in Striatal Function

Aug 1, 2003 ... The development and the function of central nervous system depend on thyroid hormones. ... Rhes / mice were viable but weighed less than wild-type mice. Furthermore, they showed behavioral abnormalities, dis- playing a gender- dependent increase ... In the central nervous system, Ras protein controls.


Reinstating Aberrant mTORC1 Activity in Huntington's Disease Mice

Dec 31, 2014 ... 4Departments of Psychiatry and Human Behavior, and Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA ... underlie the prominent striatal degeneration in HD. However, other data call to question a pathogenic role for. Rhes in HD. Rhes levels are reduced in HD patient ...


Rhes Deletion Is Neuroprotective in the 3-Nitropropionic Acid Model

Feb 27, 2013 ... Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205. Although the ... We previously reported that the striatal-enriched protein Rhes binds the mutated huntingtin protein and ... study, mice received a single IP injection of 3-NP starting at 30 mg/kg, increased daily by ...


Striatal Vulnerability in Huntington's Disease: Neuroprotection

Jun 7, 2017 ... and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity .... SNc neurons and terminates goal-directed behavior by reducing dopamine release in the matrix [70]. ..... restoring Rhes alleviates motor deficits and brain pathology in HD mice by activating autophagy.


Small G Proteins Dexras1 and RHES and Their Role in

Feb 18, 2014 ... Dexras1 and RHES, monomeric G proteins, are members of small GTPase family that are involved in modulation of .... This study suggested .... function [34]. RHES protein is expressed in different areas of the central nervous system such as striatum, olfactory tubercle, hippocampus (CA1, CA2, and CA3), ...


Dysfunctional dopaminergic neurotransmission in asocial BTBR mice

Aug 19, 2014 ... resonance imaging (fMRI), behavioural and molecular readouts to probe dopamine neurotransmission responsivity in BTBR T+. Itpr3tf/J mice ... mice, a finding that is likely to have a role in the distinctive social and behavioural deficits exhibited by these mice. ... Abnormalities in neurotransmitter pathways.


Full Text (PDF)

Feb 2, 2016 ... L-DOPA increases levels of adaptor protein p11 (S100A10) in dopa- minoceptive neurons of the striatum. ... Mice lacking p11 in dopamine D2R-containing neurons have a reduced response to L-DOPA on the ..... rons, we studied the role of p11 in a pharmacological intervention known to occur through ...


Modeling Neurodegeneration in Zebrafish

Jan 27, 2011 ... of parkin loss of function show a loss of DA neurons and reduced mitochondria with a remarkable loss of cristae [6,. 7]. However, parkin-null mice do not develop any DA neuron loss or mitochondrial or behavioral abnormality [8]. The zebrafish parkin gene encodes a 458 amino acid protein, which is highly ...


Serine 421 regulates mutant huntingtin toxicity and clearance in mice

Nov 6, 2014 ... To study the role of HTT-S421-P in a mam- malian model system, we used the BACHD mouse model of HD. BACHD mice express human mHTT with a pathogenic 97Q repeat stretch under the control of its endogenous promoter. As they age, these mice show robust behavioral and histopathological pheno-.


Post-translational modification biology of glutamate receptors and

Mar 17, 2011 ... messenger systems. ... Early studies have established that this family of receptors , including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at ... Keywords: AMPA, NMDA, mGluR, dopamine, phosphorylation, palmitoylation, ubiquitination, sumoylation.


Iron dysregulation in Huntingtons disease

The function of Rhes is not fully understood, but is known to be involved in phosphatidylinositide 3-kinases. (PI3K) activation (Vargiu et al. 2004), regulatory actions on. AKT (Protein Kinase B) pathway (Harrison et al. 2013), and modulation of dopamine receptor-mediated behavior. (Quintero et al. 2008). Rhes is selectively ...


Late-Breaking & Study Group Abstracts, Guided Poster Tour

Jun 4, 2017 ... Veterans Affairs Puget Sound Health Care System, Department of Neurology University of Washington School of. Medicine ..... behavior in animal models of PD. Methods: ... role of Rhes protein in survival of DA neurons, we have investigate neurotoxic and neuroinflammatory markers in. Rhes-/- (KO), male ...


Preservation of Striatal Cannabinoid CB1 Receptor Function

Feb 15, 2010 ... Behavioural Neuroscience Laboratory, CEINGE–Biotecnologie Avanzate, Naples , Italy (A.U.); and Dipartimento di Scienze .... related behavior. The EPM represents one of the most widely used tests for assess- ing anxiety in rodents ( Lister, 1987). Each mouse was placed in ... To study the effects of stress.


Rhes, a Striatal-selective Protein Implicated in Huntington Disease

Nov 20, 2013 ... reported that the striatal-specific protein Rhes binds mHtt and enhances its cytotoxicity. Moreover, Rhes-deleted mice are dra- matically protected from neurodegeneration and motor dys- function in mouse models of HD. We now report a function of. Rhes in autophagy, a lysosomal degradation pathway ...


The Pharmacology of L-DOPA-Induced Dyskinesia in Parkinson's

The Dopaminergic System . ..... 32 kDa; DAT, dopamine transporter; DHA, docosohexaenoic acid; EGR1, early growth response protein 1; EMA, European Medicines Agency; ... preprotachykinin; Ras-GRF1, Ras-guanine nucleotide- releasing factor 1; RBD, rapid-eye-movement sleep behavior disorder; Rhes, Ras homolog ...


Dopamine D2 receptors' effects on renal inflammation are mediated

Aug 19, 2015 ... through effects on PP2A activity/expression. dopamine D2 receptor; renal proximal tubule cells; protein phospha- tase 1A; AKT. INDEPENDENT OF INNERVATION, the kidney synthesizes dopamine that is important in the regulation of renal function and blood pressure (1). The renal dopaminergic system ...


Selective deficits in the expression of striatal-enriched mRNAs in

lesioned rats to determine their dependence on dopamine innervation. No changes in expression ... RGS9, regulator of G-protein signaling-9; Rhes, ras homolog enriched in striatum; RXR, retinoid X receptor; SCNb4, ...... decrease in striatal function implicated in this study occurs in the absence of neuronal degeneration ...