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

Notch signaling plays an important role in the process of cell-fate assignation during nervous system development. DNER is a neuron-specific transmembrane protein carrying extracellular EGF-like repeats and is expressed in somatodendritic regions. In vitro studies demonstrated that DNER mediates Notch signaling by cell-cell interaction. In the cerebellum, DNER is abundantly expressed in Purkinje cells and moderately in granule cells. DNER-knockout mice showed motor discoordination. The mutant cerebellum showed morphological impairments of Bergmann glia and multiple innervation between climbing fibers and Purkinje cells. Moreover, glutamate clearance at the synapses between parallel fibers and Purkinje cells was significantly weakened, and the expression of GLAST, a glutamate transporter in Bergmann glia, was reduced in the mutant cerebellum. Therefore, DNER contributes to the morphological and functional maturation of Bergmann glia via the Notch signaling pathway, and is essential for precise cerebellar development.
Cerebellum 2006
PMID:DNER as key molecule for cerebellar maturation. 1699 55

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease of the cerebellum caused by a polyglutamine-repeat expansion in the protein ATXN1. We have previously demonstrated that astrocytic activation occurs early in pathogenesis, correlates with disease progression, and can occur when mutant ATXN1 expression is limited to Purkinje neurons. We now show that expression of glutamate and aspartate transporter, GLAST, is decreased in cerebellar astrocytes in a mouse model of SCA1. This decrease occurs in non-cell autonomous manner late in disease and correlates well with the loss of Purkinje neurons. Astrogliosis or decreased neuronal activity does not correlate with diminished GLAST expression. In addition, Bergmann glia remain capable of transcriptional upregulation of GLAST in response to improvement in Purkinje neurons supporting the notion of active neuron-glia crosstalk in disease.
Cerebellum 2015 Feb
PMID:Decreased expression of glutamate transporter GLAST in Bergmann glia is associated with the loss of Purkinje neurons in the spinocerebellar ataxia type 1. 2525 16