Publications by authors named "Scott Mackler"
Article Synopsis
- The study investigates the phenomenon of sour ageusia, where two patients could not perceive sour tastes but still responded normally to bitter, sweet, and salty flavors.
- Biopsies were taken from the patients and sour-normal individuals, revealing that certain ion channels associated with sour taste (ASICs and PKDs) were absent in the patients but present in the controls.
- This research implies that ASICs and PKDs play a crucial role in sour taste perception, presenting the first case of sour ageusia in humans and suggesting a distinct cellular pathway for sour taste separate from other flavors.
Article Synopsis
- NAC1 is identified as a corepressor for various POZ/BTB transcriptional repressor proteins, affecting gene regulation in both neuronal and non-neuronal cells.
- In experiments, NAC1 showed the ability to reverse transcriptional inhibition caused by multiple Gal4 fusion proteins, indicating its role in modulating transcriptional activity.
- The study also revealed that NAC1 selectively interacts with other POZ/BTB proteins, confirming its involvement in protein-protein interactions, particularly in central nervous system tissues.
NAC1 is a novel member of the POZ/BTB (Pox virus and Zinc finger/Bric-a-bracTramtrack Broad complex) but varies from other proteins of this class in that it lacks the characteristic DNA-binding motif, suggesting a novel role. We have employed constitutive gene deletion to elucidate the role of NAC1 in vivo. Nac1 mutant mice are viable with no obvious developmental or physiological impairments.
View Article and Find Full Text PDFCoordinated proteolysis of synaptic proteins is required for synaptic plasticity, but a mechanism for recruiting the ubiquitin-proteasome system (UPS) into dendritic spines is not known. NAC1 is a cocaine-regulated transcriptional protein that was found to complex with proteins in the UPS, including cullins and Mov34. NAC1 and the proteasome were cotranslocated from the nucleus into dendritic spines in cortical neurons in response to proteasome inhibition or disinhibiting synaptic activity with bicuculline.
View Article and Find Full Text PDFIn this report, CoREST was identified as a protein that interacts with NAC1. NAC1 is a cocaine-regulated Pox virus and Zinc finger/Bric-a-brac Tramtrack Broad complex (POZ/BTB) repressor protein, which mediates interactions among several other transcriptional regulators. In the present study, an interaction between NAC1 and CoREST was detected in neuro-2A cells and HEK293T cells.
View Article and Find Full Text PDFOutbred rats show significant variability in their propensity to consume alcohol. These experiments were designed to examine the effect of cocaine on the expression of motor activation or place preference in outbred Wistar rats that consumed either high or low quantities of alcohol. These rats were exposed to a 2-bottle limited access procedure and dichotomized into 2 groups, high (mean 0.
View Article and Find Full Text PDFArticle Synopsis
- NAC1 expression increases in the nucleus accumbens of rats after cocaine withdrawal, suggesting it serves as a compensatory mechanism against cocaine's effects.
- Studies show NAC1 behaves as a transcriptional regulator but is also found diffusely in the cytoplasm of neural cells, not just the nucleus.
- Phosphorylation of a specific residue by PKC is crucial for this diffuse expression, hinting at a possible non-transcriptional role for NAC1 in brain function.
Article Synopsis
- Repeated cocaine exposure leads to long-term behavioral changes in mammals, including increased locomotor activity known as behavioral sensitization, linked to specific molecular changes.
- Research focused on NAC1, a transcription factor with two isoforms, found increased expression in the nucleus accumbens of rats after cocaine use, particularly the long isoform (lNAC1) and short isoform (sNAC1).
- The increase in NAC1 expression correlates with decreased behavioral sensitization over time, suggesting NAC1 could act as an endogenous inhibitor of this sensitization and serves as a potential target for future studies on cocaine's effects.
POZ/BTB proteins influence cellular development and in some examples act as oncoproteins. However, several POZ/BTB transcription factors have been found in terminally differentiated neurons, where their functions remain unknown. One example is NAC1, a constitutively-expressed protein that can regulate behaviors associated with cocaine use.
View Article and Find Full Text PDFComorbid abuse of and dependency on multiple drugs is a common occurrence clinically. We have developed an animal model that provides rats with the opportunity to choose, through oral consumption, between concurrently available ethanol and cocaine with water also available. This provides the ability to screen for the effectiveness of potential pharmacotherapeutic agents on the baseline consumption of both drugs.
View Article and Find Full Text PDFWe recently reported that 6-beta naltrexol, the major metabolite of naltrexone in humans, reduced ethanol consumption in rats. Two new experiments were designed to compare 6-beta naltrexol and naltrexone across three dose levels on an ethanol or sucrose baseline using a limited-access procedure in Wistar rats. The results of Experiment 1 showed that both 6-beta naltrexol and naltrexone reduced ethanol consumption across a range of doses.
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