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Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor
TLDR
It is hypothesized that cannabidiol would inhibit cannabinoid agonist activity through negative allosteric modulation of CB1 receptors through positive allosterics modulation ofCB1 receptors. Expand
Type 1 Cannabinoid Receptor Ligands Display Functional Selectivity in a Cell Culture Model of Striatal Medium Spiny Projection Neurons*
TLDR
These data demonstrate that individual cannabinoids display functional selectivity at CB1 leading to activation of distinct signaling pathways, which may be exploited to maximize therapeutic efficacy. Expand
Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington′s disease transgenic mice prior to the onset of motor symptoms
TLDR
The finding that steady-state mRNA levels of two members of the phosphodiesterase (PDE) multi-gene family decrease over time in the striatum of R6 transgenic HD mice relative to age-matched wild-type littermates suggests that the regulation of PDE10A and PDE1B, but not PDE4A, mRNA levels is dependent on the relative expression of or number of CAG repeats within the human HD transgene. Expand
Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice.
TLDR
A recombinant adeno-associated viral serotype 5 (rAAV5) gene transfer strategy to posttranscriptionally suppress the levels of striatal mutant huntingtin (mHtt) in the R6/1 HD transgenic mouse via RNA interference suggests that a reduction in the levelsof striatal mHtt can ameliorate the HD phenotype of R 6/1 mice. Expand
Mutant huntingtin affects the rate of transcription of striatum‐specific isoforms of phosphodiesterase 10A
Huntington's disease (HD) is caused by the inheritance of a copy of the gene encoding mutant huntingtin with an expanded CAG repeat. Phosphodiesterase 10A (PDE10A) mRNA decreases in transgenic HDExpand
Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol‐dimethylheptyl at the type 1 and type 2 cannabinoid receptors
We sought to understand why (−)‐cannabidiol (CBD) and (−)‐cannabidiol‐dimethylheptyl (CBD‐DMH) exhibit distinct pharmacology, despite near identical structures.
Structure, expression and regulation of the cannabinoid receptor gene (CB1) in Huntington's disease transgenic mice.
TLDR
The progressive decline in CB1 mRNA levels in R6 compared to wild-type mice was due to decreased transcription, which is consistent with the hypothesis that mutant huntingtin exerts its effects by altering transcription factor activity. Expand
Complete sequence of the mitochondrial DNA of Chlamydomonas eugametos
TLDR
The deep evolutionary divergence between these two Chlamydomonas taxa within the Chlorophyceae suggests that their shared features of mitochondrial genome organization evolved prior to the origin of this group. Expand
Cannabinoid receptor messenger RNA levels decrease in a subset of neurons of the lateral striatum, cortex and hippocampus of transgenic Huntington’s disease mice
TLDR
The results demonstrate that the single copy cannabinoid receptor gene is subjected to cell-specific and time-dependent regulation of the steady-state level of its gene product as a result of the expression of the Huntington's disease gene. Expand
Biased Type 1 Cannabinoid Receptor Signaling Influences Neuronal Viability in a Cell Culture Model of Huntington Disease
TLDR
Enhancing Gαi/o-biased endocannabinoid signaling may be therapeutically beneficial in HD, whereas cannabinoids that are β-arrestin-biased—such as THC found at high levels in modern varieties of marijuana—may be detrimental to CB1 signaling, particularly in HD where CB1 levels are already reduced. Expand
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