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)

Several studies point to the importance of peptides and proteolysis in Alzheimer's disease (AD). Because of its ability to study small proteins and peptides, reverse-phase HPLC was employed to study these species in AD. Cerebellum was chosen for these initial studies because it does not show significant neuronal loss but does show some pathology in AD. Examination of over 600 peptide peaks per case revealed 15 that were elevated in AD. Nine were fragments of hemoglobin, and the remainder included two species of calmodulin, two of myelin basic protein, and one each of 67 kDa neurofilament protein and PEP-19. The cleavage sites on hemoglobin were after hydrophobic residues and immunolocalization was seen preferentially around blood vessel walls and granule cells. The elevation of the non-serum-derived peptides was characteristic of general metabolic changes that occurred in AD cerebellum, and the presence of elevated hemoglobin polypeptides indicated either possible disruption of the blood-brain barrier or selective evasion of it by peptidaceous products. Further studies are required to establish whether hemoglobin fragments have a role in neurodegenerative processes such as AD.
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PMID:Increased levels of hemoglobin-derived and other peptides in Alzheimer's disease cerebellum. 751 35

The cerebellar Purkinje cells (P-cells) comprise an organelle that is suitable for combined analysis by morphology and genomics, using biophysical tools. In some unknown way, genomic information specifies the development of P-cells. One of us (AJP) has previously proposed that fractal processes associated with DNA are in a causal relation to the fractal properties of organelles such as P-cells (FractoGene, 2002, patent pending). This fractal postulate predicts that the dendritic arborization of P-cells will be less complex in lower order vertebrates. The prediction can be tested by systematic comparative neuroanatomy of the P-cell in species for which genome sequences permit inter-species comparison. The Fugu rubripes (Fugu), Danio rerio (Danio) and other species are lower order vertebrates for which genome sequences are available and tests could be conducted. Consistent with the fractal prediction, P-cell dendritic arbor is primitive in Fugu, being much less complex than in Mus musculus and in Homo sapiens. Genomic analysis readily identified PEP19/Pcp4, Calbindin-D28k, and GAD67 genes in Fugu and in Danio that are closely associated with P-cells in Canis familiaris, Rattus norvegicus, Mus musculus and Homo sapiens. Gene L7/Pcp2 exhibits strongest association with P-cells in higher vertebrates. L7/Pcp2 shows strong protein residue homology with genes greater than 600 residues and including 2-3 GoLoco domains, designated as having G protein signaling modulator function (AGS3-like proteins). Fugu has a short gene with a single GoLoco domain, but it has greatest homology with the AGS3-like proteins. No similar short gene is present in Danio or in Xenopus. Classical L7/Pcp2 is only detected in higher vertebrates, suggesting that it may be a marker of more recent evolutionary development of cerebellar P-cells. We expect that a new generation of data mining tools will be required to support recursive fractal geometrical, combinatorial, and neural network models of the genomic basis of morphogenesis.
Cerebellum 2006
PMID:Genomics, morphogenesis and biophysics: triangulation of Purkinje cell development. 1652 61

Among ten sodium channel alpha-subunit genes mapped in human and mouse genomes, the SCN8A gene is primarily expressed in neurons and glia. Mice with two types of Scn8a null mutations--Scn8a ( med ) and Scn8a ( medTg )--live for only 21-24 days, but those with incomplete mutations-Scn8a ( medJ ) and Scn8a ( medJo )--and those with knockout of Scn8a only in cerebellar Purkinje cells live to adult age. We review here previous work on cerebellum and related regions of Scn8a mutant mice and include some newer immunohistochemical and microchemical results. The resurgent sodium current that underlies the repeated firing of Purkinje cells is reduced in Scn8a mutant and knockout mice. Purkinje cells of mutant mice have greatly reduced spontaneous activity, as do the analogous cartwheel cells of the dorsal cochlear nucleus. Up-regulation of GABA(A) receptors in regions to which Purkinje cells project may partially compensate for their decreased activity in the mutant mice. The somata of cerebellar Purkinje cells of Scn8a ( medJ ) and Scn8a ( medJo ) mice, as revealed by PEP-19 immunoreaction, are slightly smaller than normal, and their axons, especially in Scn8a ( medJo ) mice, sometimes show enlargements similar to those in other types of mutant mice. Density of GABA-like immunoreactivity is decreased in Purkinje somata and regions of termination in deep cerebellar and vestibular nuclei of Scn8a ( medJ ) mice, but measured GABA concentration is not significantly reduced in microdissected samples of these regions. The concentrations of taurine and glutamine are significantly increased in cerebellar-related regions of Scn8a ( medJ ) mice, possibly suggesting up-regulation of glial amino acid metabolism.
Cerebellum 2009 Sep
PMID:Cerebellum-related characteristics of Scn8a-mutant mice. 1942 68