Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse Anp32e (Acidic leucine-rich nuclear phosphoprotein 32 family, member e: NM_023210, P97822, formerly Cpd1), a protein identified in postnatal cerebellum by differential display, belongs to the superfamily of leucine rich repeat (LRR) proteins and to the Acidic Nuclear Phosphoprotein 32 (ANP32) family of protein phosphatase 2 (PPP2, formerly PP2A) inhibitors. Two families of PPP2 inhibitor proteins have been described, ANP32 and SET, represented by the human proteins ANP32A (NM_006305, formerly LANP, PP32, I1PPP2, PHAPI, MAPM, mapmodulin) and SET (NM_003011, formerly PHAPII, 2PPP2, I2PPP2, TAF-1BETA). Besides their common PPP2 inhibitor activity, described several years ago, these nucleo-cytoplasmic shuttling phosphoproteins have additional and very important functions recently reported. In HeLa cells, ANP32A, SET (isoforms A and B) and ANP32B (APRIL), form a multi-subunit heterocomplex with ELAVL1 (NM_001419, formerly HuR), a protein that stabilizes short-lived mRNAs containing AU-rich elements (AREs). A similar heterocomplex, formed by SET (A and B) and ANP32A as major subunits, possess histone acetyltransferase inhibitory activity (INHAT), and have a role in chromatin remodeling and transcriptional regulation (histone code). The possible roles of these multifunctional proteins are discussed here, with emphasis on mouse Anp32e and the cerebellar tissue.
Cerebellum 2003
PMID:Anp32e (Cpd1) and related protein phosphatase 2 inhibitors. 1496 90

Histone deacetylases (HDACs) are epigenetic regulatory proteins that repress gene transcription by changing DNA conformation. The regulation of gene expression through histone deacetylation is an important mechanism for the development of the central nervous system. Although the disruption of the balance in epigenetic gene regulation has been implicated in many CNS developmental abnormalities and diseases, the expression pattern of HDACs in various cell types in the brain during its maturation process has had limited exploration. Therefore, in this study, we investigate the cell type-specific and developmental stage-specific expression pattern of HDAC1 and HDAC2 in the mouse cerebellum. Our experimental results show that the cerebellar progenitors and glial cells express high levels of HDAC1 and low levels of HDAC2. On the other hand, the post-mitotic migrating neuronal cells of the cerebellar cortex show strong HDAC2 and weak HDAC1 expressions. In more differentiated neuronal cells, including Purkinje cells, granule cells, unipolar brush cells, and GABAergic interneurons, we found a consistent expression pattern, high levels of HDAC2 and low levels of HDAC1. Therefore, our data provide support for the potential important roles of HDAC1 in cell proliferation and HDAC2 in migration and differentiation.
Cerebellum 2013 Aug
PMID:The expression of HDAC1 and HDAC2 during cerebellar cortical development. 2343 26

Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new therapy to manage cerebellar disorders associated with hyperexcitatory CNS disorders like ethanol withdrawal.
Cerebellum 2015 Aug
PMID:Alcohol Withdrawal and Cerebellar Mitochondria. 2519 4

Epigenetics is the process by which gene expression is regulated by events other than alterations of the genome. This includes DNA methylation, histone modifications, chromatin remodeling, microRNAs, and long non-coding RNAs. Methylation of DNA, chromatin remodeling, and histone modifications regulate the chromatin and access of transcription factors to DNA and in turn gene transcription. Alteration of chromatin is now recognized to be deregulated in many cancers. Medulloblastoma is an embryonal tumor of the cerebellum and the most common malignant brain tumor in children, that occurs only rarely in adults. Medulloblastoma is characterized by four major molecularly and histopathologically distinct groups, wingless (WNT), sonic hedgehog (SHH), group 3 (G3), and group 4 (G4), that, except for WNT, are each now subdivided in several subgroups. Gene expression array, next-generation sequencing, and methylation profiling of several hundred primary tumors by several consortia and independent groups revealed that medulloblastomas harbor a paucity of mutations most of which occur in epigenetic regulators, genetic alterations in oncogenes and tumor suppressors, in addition to copy number alterations and chromosome gains and losses. Remarkably, some tumors have no reported mutations, suggesting that some genes required for oncogenesis might be regulated by epigenetic mechanisms which are still to be uncovered and validated. This review will highlight several epigenetic regulators focusing mainly on histone modifiers identified in medulloblastoma.
Cerebellum 2018 02
PMID:Epigenetic Drivers in Pediatric Medulloblastoma. 2917 21

Autism spectrum disorders (ASDs) are neuropsychiatric diseases characterized by impaired social interaction, communication deficits, and repetitive and stereotyped behaviors. ASD etiology is unknown, and both genetic and environmental causes have been proposed. Different brain structures are believed to play a role in ASD-related behaviors, including medial prefrontal cortex (mPFC), hippocampus, piriform cortex (Pir), basolateral amygdala (BLA) and Cerebellum. Compelling evidence suggests a link between white matter modifications and ASD symptoms in patients. Besides, an hypomyelination of the mPFC has been associated in rodents to social behavior impairment, one of the main symptoms of ASD. However, a comparative analysis of myelination as well as oligodendroglial (OL)-lineage cells in brain regions associated to social behaviors in animal models of ASD has not been performed so far. Here, we investigated whether OL-lineage cells and myelination are altered in a murine model of ASD induced by the prenatal exposure to valproic acid (VPA). We showed an hypomyelination in the BLA and Pir of adult VPA-exposed mice. These results were accompanied by a decrease in the number of OL-lineage cells and of mature OLs in the Pir, in addition to the mPFC, where myelination presented no alterations. In these regions the number of oligodendrocyte progenitors (OPCs) remained unaltered. Likewise, activation of histone deacetylases (HDACs) on OL-lineage cells in adulthood showed no differences. Overall, our results reveal OL-lineage cell alterations and hypomyelination as neuropathological hallmarks of ASD that have been overlooked so far.
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PMID:Hypomyelination and Oligodendroglial Alterations in a Mouse Model of Autism Spectrum Disorder. 3068 9