Dopamine D1 receptor–mediated aggregation of N-terminal fragments of mutant huntingtin and cell death in a neuroblastoma cell line

Robinson, Pierre; Lebel, Manon; Cyr, Michel

doi:10.1016/j.neuroscience.2008.02.052

Cited by 16 publications

(17 citation statements)

References 58 publications

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“…Furthermore, the same result was found with forskolin, which directly activates AC, further implicating the D 1 receptor signal transduction pathway in the aggregation of mHTT (Fig. 3) [202, 203]. …”

Section: Dopamine Modulationsupporting

confidence: 61%

“…Pharmacological activation of D 1 receptors, for example, accelerates the formation of mHTT nuclear aggregates, and again the effect is mediated by the activation of transcription factors [202]. Furthermore, the same result was found with forskolin, which directly activates AC, further implicating the D 1 receptor signal transduction pathway in the aggregation of mHTT (Fig.…”

Section: Dopamine Modulationsupporting

confidence: 55%

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Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

Rangel‐Barajas

Rebec

2016

JHD

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Aberrant communication between striatum, the main information processing unit of the basal ganglia, and cerebral cortex plays a critical role in the emergence of Huntington’s disease (HD), a fatal monogenetic condition that typically strikes in the prime of life. Although both striatum and cortex undergo substantial cell loss over the course of HD, corticostriatal circuits become dysfunctional long before neurons die. Understanding the dysfunction is key to developing effective strategies for treating a progressively worsening triad of motor, cognitive, and psychiatric symptoms. Cortical output neurons drive striatal activity through the release of glutamate, an excitatory amino acid. Striatal outputs, in turn, release γ-amino butyric acid (GABA) and exert inhibitory control over downstream basal ganglia targets. Ample evidence from transgenic rodent models points to dysregulation of corticostriatal glutamate transmission along with corresponding changes in striatal GABA release as underlying factors in the HD behavioral phenotype. Another contributor is dysregulation of dopamine (DA), a modulator of both glutamate and GABA transmission. In fact, pharmacological manipulation of DA is the only currently available treatment for HD symptoms. Here, we review data from animal models and human patients to evaluate the role of DA in HD, including DA interactions with glutamate and GABA within the context of dysfunctional corticostriatal circuitry.

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Section: Dopamine Modulationsupporting

confidence: 61%

Section: Dopamine Modulationsupporting

confidence: 55%

Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

Rangel‐Barajas

Rebec

2016

JHD

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“…In addition, activation of the D1 dopamine receptor accelerates the formation of mutant huntingtin nuclear aggregates in SK-N-MC neuroblastoma cells (Robinson et al, 2008). Overstimulation of ionotropic neurotransmitter receptors, in particular glutamate receptors, is well known to exert adverse excitotoxic effects (Choi, 1987).…”

Section: Metabotropic Neurotoxicity Of Camp-mediated Dopamine Receptormentioning

confidence: 99%

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

2011

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“…Dopaminergic input to the striatum, which potentiates glutamate excitotoxicity (Cepeda et al, 1998; Tang et al, 2007), also affects proteostasis. Dopamine can increase IB formation in primary neuron cultures and cell lines (Charvin et al, 2005; Robinson et al, 2008), suggesting that projections from the cortex and substantia nigra to the striatum may promote striatal susceptibility in HD by altering striatal proteostasis mechanisms ( Figure 1 ).…”

Section: Synaptic Activity Regulates Proteostasismentioning

confidence: 99%

Proteostasis in striatal cells and selective neurodegeneration in Huntingtonâ€™s disease

Margulis

Finkbeiner

2014

Front. Cell. Neurosci.

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Selective neuronal loss is a hallmark of neurodegenerative diseases, including Huntington’s disease (HD). Although mutant huntingtin, the protein responsible for HD, is expressed ubiquitously, a subpopulation of neurons in the striatum is the first to succumb. In this review, we examine evidence that protein quality control pathways, including the ubiquitin proteasome system, autophagy, and chaperones, are significantly altered in striatal neurons. These alterations may increase the susceptibility of striatal neurons to mutant huntingtin-mediated toxicity. This novel view of HD pathogenesis has profound therapeutic implications: protein homeostasis pathways in the striatum may be valuable targets for treating HD and other misfolded protein disorders.

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Dopamine D1 receptor–mediated aggregation of N-terminal fragments of mutant huntingtin and cell death in a neuroblastoma cell line

Cited by 16 publications

References 58 publications

Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

Proteostasis in striatal cells and selective neurodegeneration in Huntingtonâ€™s disease

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