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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor that can inhibit proliferation and migration and controls apoptosis in a number of cell types, mainly through inhibition of the phosphoinositide 3-kinase (PI3K) signaling pathway. Patients carrying inactivating mutations of PTEN show a prevalence to develop tumors that can coincide with neurological defects such as mental retardation, ataxia and seizures. A number of in vitro and in vivo studies were instrumental in uncovering a direct correlation between deregulated PI3K/PTEN signaling and changes in neuronal morphogenesis, which is likely to have profound bearings upon the pathogenesis of neurological symptoms. This review outlines recent work on the function of PTEN during vertebrate brain development and the current understanding of the signaling pathways downstream of PTEN that control neuronal connectivity in the brain.
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PMID:Function of PTEN during the formation and maintenance of neuronal circuits in the brain. 1807 55

The phosphatidylinositol 3-kinase (PI3K) signaling pathway modulates growth, proliferation and cell survival in diverse tissue types and plays specialized roles in the nervous system including influences on neuronal polarity, dendritic branching and synaptic plasticity. The tumor-suppressor phosphatase with tensin homology (PTEN) is the central negative regulator of the PI3K pathway. Germline PTEN mutations result in cancer predisposition, macrocephaly and benign hamartomas in many tissues, including Lhermitte-Duclos disease, a cerebellar growth disorder. Neurological abnormalities including autism, seizures and ataxia have been observed in association with inherited PTEN mutation with variable penetrance. It remains unclear how loss of PTEN activity contributes to neurological dysfunction. To explore the effects of Pten deficiency on neuronal structure and function, we analyzed several ultra-structural features of Pten-deficient neurons in Pten conditional knockout mice. Using Golgi stain to visualize full neuronal morphology, we observed that increased size of nuclei and somata in Pten-deficient neurons was accompanied by enlarged caliber of neuronal projections and increased dendritic spine density. Electron microscopic evaluation revealed enlarged abnormal synaptic structures in the cerebral cortex and cerebellum. Severe myelination defects included thickening and unraveling of the myelin sheath surrounding hypertrophic axons in the corpus callosum. Defects in myelination of axons of normal caliber were observed in the cerebellum, suggesting intrinsic abnormalities in Pten-deficient oligodendrocytes. We did not observe these abnormalities in wild-type or conditional Pten heterozygous mice. Moreover, conditional deletion of Pten drastically weakened synaptic transmission and synaptic plasticity at excitatory synapses between CA3 and CA1 pyramidal neurons in the hippocampus. These data suggest that Pten is involved in mechanisms that control development of neuronal and synaptic structures and subsequently synaptic function.
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PMID:Phosphatase and tensin homolog, deleted on chromosome 10 deficiency in brain causes defects in synaptic structure, transmission and plasticity, and myelination abnormalities. 1808 64

A 4-year-old Dutch warmblood mare was presented with a 10-month history of ataxia and proprioceptive deficits. Computed tomography defined a large, non-contrast enhancing mass in the left cerebral hemisphere. Necropsy examination revealed a tumour that effaced much of the piriform and temporal lobes. Microscopically the lesion was classified as a grade IV glioblastoma with an oligodendroglial component (GBM-O). The tumour was composed of highly pleomorphic cells organized in different patterns within a fibrillary stroma. There were multiple foci of necrosis. At the periphery of the tumour neoplastic oligodendroglioma-like cells were embedded in an extracellular mucinous matrix. Most neoplastic cells were strongly immunoreactive for glial fibrillary acidic protein; however, the oligodendroglioma cells did not express this marker. Cells forming microvascular proliferations were positively labelled for expression of factor VIII and smooth muscle actin. All neoplastic cells were negative for Neu-N and synaptophysin. The proliferation index was up to 5%. All neoplastic cells and normal brain tissue from the horse were uniformly negative for expression of epidermal growth factor receptor (EGFR), EGFR vIII mutant and the phosphatase and tensin homologue (PTEN) compared with positive control human GBM tissue. To our knowledge this is the first report of a GBM-O in the horse.
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PMID:A grade IV glioblastoma with an oligodendroglial component (GBM-O) in a horse. 1989 10

Well-differentiated thyroid cancer accounts for 95% of thyroid malignancies. In contrast to medullary thyroid carcinoma, in which about 25% are familial, only 5% of follicular cell-derived thyroid carcinomas are a component of a familial cancer syndrome. The familial follicular cell-derived tumors or nonmedullary thyroid carcinoma encompass a heterogeneous group of diseases, and are classified into 2 distinct groups: syndromic-associated tumors, occurring in syndromes in which nonmedullary thyroid carcinomas are the predominant tumor encountered, and nonsyndromic tumors, those occurring in tumor syndromes in which thyroid involvement is a minor component. The first group, syndromic-associated tumors, includes phosphase and tensin (PTEN)-hamartoma tumor syndrome/Cowden syndrome, familial adenomatous polyposis/Gardner syndrome, Carney complex type 1, Werner syndrome, and Pendred syndrome. Other syndromes, as McCune Albright syndrome, Peutz-Jeghers syndrome, and Ataxia-teleangiectasia syndrome may be associated with the development of follicular cell-derived tumors, but the link is less established than the above syndromes. The syndromic-associated tumors are the focus of this review. The second group of familial follicular cell-derived tumors syndromes or nonsyndromic tumors, in which nonmedullary thyroid carcinomas are the major findings, include pure familial papillary thyroid carcinoma, with or without oxyphilia, familial papillary thyroid carcinoma with papillary renal cell carcinoma, and familial papillary thyroid carcinoma with multinodular goiter. This review will discuss the clinical and pathological findings of the patients with familial syndrome-associated tumors: PTEN-hamartoma tumor syndrome/Cowden syndrome, familial adenomatous polyposis syndrome, Carney complex type 1, Werner syndrome, and Pendred syndrome.
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PMID:Thyroid cancer of follicular cell origin in inherited tumor syndromes. 2096 48