Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0036341 (
schizophrenia
)
60,220
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The etiology of bipolar disorder (BD) is unknown and the neurobiological underpinnings are not fully understood. Both genetic and environmental factors contribute to the risk of BD, which may be linked through epigenetic mechanisms, including those regulated by
histone deacetylase
(
HDAC
) enzymes. This study measures in vivo
HDAC
expression in individuals with BD for the first time using the
HDAC
-specific radiotracer [
11
C]Martinostat. Eleven participants with BD and 11 age- and sex-matched control participants (CON) completed a simultaneous magnetic resonance - positron emission tomography (MR-PET) scan with [
11
C]Martinostat. Lower [
11
C]Martinostat uptake was found in the right amygdala of BD compared to CON. We assessed uptake in the dorsolateral prefrontal cortex (DLPFC) to compare previous findings of lower uptake in the DLPFC in
schizophrenia
and found no group differences in BD. Exploratory whole-brain voxelwise analysis showed lower [
11
C]Martinostat uptake in the bilateral thalamus, orbitofrontal cortex, right hippocampus, and right amygdala in BD compared to CON. Furthermore, regional [
11
C]Martinostat uptake was associated with emotion regulation in BD in fronto-limbic areas, which aligns with findings from previous structural, functional, and molecular neuroimaging studies in BD. Regional [
11
C]Martinostat uptake was associated with attention in BD in fronto-parietal and temporal regions. These findings indicate a potential role of HDACs in BD pathophysiology. In particular,
HDAC
expression levels may modulate attention and emotion regulation, which represent two core clinical features of BD.
...
PMID:In vivo human brain expression of histone deacetylases in bipolar disorder. 3264 95
Collapsin response mediator proteins (CRMPs) are ubiquitously expressed in neurons from worms to humans. A cardinal feature of CRMPs is to mediate growth cone collapse in response to Semaphorin-3A signaling through interactions with cytoskeletal proteins. These are critical regulatory roles that CRMPs play during neuritogenesis and neural network formation. Through post-translational modifications, such as phosphorylation, O-GlcNAcylation, SUMOylation, and proteolytic cleavage, CRMPs participate in synaptic plasticity by modulating NMDA receptors, L- and N-type voltage-gated calcium channels (VGCCs), thus affecting neurotransmitter release. CRMPs also possess
histone deacetylase
(
HDAC
) activity, which deacetylates histone H4 during neuronal death. Calcium-dependent proteolytic cleavage of CRMPs results in the truncation of CRMPs, producing a large 54 kD fragment (p54). Translocation of the p54 fragment into the nucleus leads to deacetylation of nuclear histone H4 and de-repression of transcription factor E2F1 expression. Increased expression of E2F1 elevates the expression of genes in cell cycle and death. These new and exciting studies lead to the realization that CRMPs are multifunctional proteins with both regulatory and enzymatic functions. Increasing numbers of studies associate these functions of CRMPs with the development of mental and neurological disorders, such as
schizophrenia
, Alzheimer's diseases, brain trauma, and stroke. This review focuses on new evidence showing the regulatory and enzymatic functions of CRMPs and highlights recent understandings of CRMPs' roles in neurological diseases.
...
PMID:The regulatory and enzymatic functions of CRMPs in neuritogenesis, synaptic plasticity, and gene transcription. 3265 66
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