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)

Prion protein (PrP(c)) is a cell membrane glycoprotein particularly abundant in the synapses. Prion diseases are characterized by the replacement of the normal PrPc by a protease-resistant, sheet-containing isoform (PrP(CJD), PrP(Sc), PrP(BSE)) that is pathogenic. Creutzfeldt-Jakob disease (CJD) in humans, scrapie (Sc) in sheep and goats, and bovine spongiform encephalopathy (BSE) in cattle are typical prion diseases. Classical CJD can be presented as sporadic, infectious or familial, whereas the new variant of CJD (nvCJD) is considered a BSE-derived human disease. Spongiform degeneration, glial proliferation, involving astrocytes and microglia, neuron loss and abnormal PrP deposition are the main neuopathological findings in most human and animal prion diseases. Yet recent data point to synapses as principal targets of abnormal PrP deposition. Loss of synapses is an early abnormality in experimental scrapie. Decreased expression of crucial proteins linked to exocytosis and neurotransmission, covering synaptophysin, synaptosomal-associated protein of 25,000 mol wt (SNAP-25), synapsins, syntaxins and Rab3a occurs in the cerebral cortex and cerebellum in sporadic CJD. Moreover, impairment of glomerular synapses and attenuation of parallel fiber pre-synaptic terminals on Purkinje cell dendrites is a cardinal consequence of abnormal PrP metabolism in CJD. Accumulation of synaptic proteins in the soma and axonal torpedoes of Purkinje cells suggests additional impairment of axonal transport. Increase in nuclear DNA vulnerability leading to augmented numbers of cells bearing nuclear DNA fragments is a common feature in the brains of humans affected by prion diseases examined at post-mortem, but also in archival biopsy samples processed with the method of in situ end-labeling of nuclear DNA fragmentation. This form of cell death is reminiscent of apoptosis found in experimental scrapie in rodents. It is not clear that all forms of cell death in human and animal prion diseases are due to apoptosis. Yet new observations have shown cleaved (active) caspase-3 (17 kDa), a main executioner of apoptosis, expressed in scattered cells in the brains of mice with experimental scrapie and in the cerebellum of patients with sporadic CJD. Together, these data suggest activation of the caspase pathway of apoptosis in human and animal prion diseases.
Cerebellum 2002 Jul
PMID:Synaptic pathology and cell death in the cerebellum in Creutzfeldt-Jakob disease. 1287 83

A variety of missense mutations and a stop mutation in the gene coding for transmembrane protein 240 (TMEM240) have been reported to be the causative mutations of spinocerebellar ataxia 21 (SCA21). We aimed to investigate the expression of TMEM240 protein in mouse brain at the tissue, cellular, and subcellular levels. Immunofluorescence labeling showed TMEM240 to be expressed in various areas of the brain, with the highest levels in the hippocampus, isocortex, and cerebellum. In the cerebellum, TMEM240 was detected in the deep nuclei and the cerebellar cortex. The protein was expressed in all three layers of the cortex and various cerebellar neurons. TMEM240 was localized to climbing, mossy, and parallel fiber afferents projecting to Purkinje cells, as shown by co-immunostaining with VGLUT1 and VGLUT2. Co-immunostaining with synaptophysin, post-synaptic fractionation, and confirmatory electron microscopy showed TMEM240 to be localized to the post-synaptic side of synapses near the Purkinje-cell soma. Similar results were obtained in human cerebellar sections. These data suggest that TMEM240 may be involved in the organization of the cerebellar network, particularly in synaptic inputs converging on Purkinje cells. This study is the first to describe TMEM240 expression in the normal mouse brain.
Cerebellum 2020 Jun
PMID:The TMEM240 Protein, Mutated in SCA21, Is Expressed in Purkinje Cells and Synaptic Terminals. 3200 1