Publications de Ozgün Gökce | EPFL Graph Search

A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease

Protein acetylation, which is central to transcriptional control as well as other cellular processes, is disrupted in Huntington's disease (HD). Treatments that restore global acetylation levels, such as inhibiting histone deacetylases (HDACs), are effecti ...

Oxford University Press2014

Fused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity

Ozgün Gökce, Davide Franceschini

Here, we describe the selection and optimization of a chemical series active in both a full-length and a fragment-based Huntington's disease (HD) assay. Twenty-four thousand small molecules were screened in a phenotypic HD assay, identifying a series of co ...

Amer Chemical Soc2013

Decreased Striatal RGS2 Expression Is Neuroprotective in Huntington's Disease (HD) and Exemplifies a Compensatory Aspect of HD-Induced Gene Regulation

Ozgün Gökce

Background: The molecular phenotype of Huntington's disease (HD) is known to comprise highly reproducible changes in gene expression involving striatal signaling genes. Here we test whether individual changes in striatal gene expression are capable of miti ...

Public Library of Science2011

SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis

Ozgün Gökce, Heike Runne

Huntington's disease (HD), an incurable neurodegenerative disorder, has a complex pathogenesis including protein aggregation and the dysregulation of neuronal transcription and metabolism. Here, we demonstrate that inhibition of sirtuin 2 (SIRT2) achieves ...

National Academy of Sciences2010

Diminished activity-dependent brain-derived neurotrophic factor expression underlies cortical neuron microcircuit hypoconnectivity resulting from exposure to mutant huntingtin fragments

Henry Markram, Michele Giugliano, Elena Katsyuba, Ozgün Gökce, Heike Runne, Luca Gambazzi

Although previous studies of Huntington's disease (HD) have addressed many potential mechanisms of striatal neuron dysfunction and death, it is also known, based on clinical findings, that cortical function is dramatically disrupted in HD. With respect to ...

American Society for Pharmacology and Experimental Therapeutics2010

Decreased Lin7b expression in layer 5 pyramidal neurons may contribute to impaired corticostriatal connectivity in huntington disease

Ozgün Gökce, Doris Chau Voo Thu

Motor dysfunction, cognitive impairment, and regional cortical atrophy indicate cerebral cortical involvement in Huntington disease (HD). To address the hypothesis that abnormal corticostriatal connectivity arises from polyglutamine-related alterations in ...

Lippincott, Williams & Wilkins2010

Effects of BDNF and other neuroprotectants on the neuropathology of Huntington's disease

Ozgün Gökce

Huntington's disease is an autosomal dominantly inherited neurodegenerative disorder characterized by progressive motor dysfunction, dementia, psychiatric symptoms, and weight loss, eventually leading to death. Postmortem analysis of the brains of HD patie ...

EPFL2009

Short-term striatal gene expression responses to brain-derived neurotrophic factor are dependent on MEK and ERK activation

Ozgün Gökce, Heike Runne

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is believed to be an important regulator of striatal neuron survival, differentiation, and plasticity. Moreover, reduction of BDNF delivery to the striatum has been implicated in the pathophysiology of H ...

Public Library of Science2009

Diminished hippocalcin expression in Huntington's disease brain does not account for increased striatal neuron vulnerability as assessed in primary neurons

Ozgün Gökce, Nikita Rudinskiy, Nicole Déglon

Hippocalcin is a neuronal calcium sensor protein previously implicated in regulating neuronal viability and plasticity. Hippocalcin is the most highly expressed neuronal calcium sensor in the medium spiny striatal output neurons that degenerate selectively ...

Wiley-Blackwell2009

Dysregulation of gene expression in primary neuron models of Huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry

Patrick Aebischer, Valérie Gafner, Ozgün Gökce, Nicole Déglon, Heike Runne, Diana Zala

Gene expression changes are a hallmark of the neuropathology of Huntington's disease (HD), but the exact molecular mechanisms of this effect remain uncertain. Here, we report that in vitro models of disease comprised of primary striatal neurons expressing ...

2008