PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Heredodegenerative Disorders, Nervous System”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed2004

Fibroblast growth factor receptor 1 is required for the proliferation of hippocampal progenitor cells and for hippocampal growth in mouse.

Fibroblast growth factor receptor 1 (Fgfr1) is expressed at high levels by progenitor cells of the ventricular zone (VZ) within the hippocampal primordium. To investigate the role of Fgfr1 in these cells, in vivo Cre recombination of "floxed" Fgfr1 alleles was directed to cells of the radial glial lineage by using the human glial fibrillary acidic protein promoter. Radial glial-like cells of the hippocampal VZ are the progenitors of pyramidal neurons and granule cells of hippocampal dentate gyrus (DG). Mice carrying null Fgfr1 alleles (Fgfr1(Deltaflox)) in cells of this lineage showed a dramatic loss of Fgfr1 gene expression throughout the embryonic dorsal telencephalon. These Fgfr1(Deltaflox) mice exhibited a approximately 30% decrease in dividing radial glial progenitor cells in the hippocampal VZ and DG in the late embryonic period, progressing to a approximately 50-60% loss at birth, without any changes in cell survival. In addition, no FGF2-sensitive neural stem cells could be isolated from the Fgfr1(Deltaflox) hippocampal neuroepithelium, whereas epidermal growth factor-sensitive neural stem cells were not affected. The number of hippocampal pyramidal neurons and DG granule cells was approximately 30-50% decreased from the perinatal period through adulthood, and the number of parvalbumin-containing interneurons was similarly decreased in both the DG and pyramidal cell fields. We conclude that Fgfr1 is necessary for hippocampal growth, because it promotes the proliferation of hippocampal progenitors and stem cells during development.

Animals↗
PubMed2006

Beta-amyloid, oxidative stress and down syndrome.

Down syndrome (DS) provides a model for studying important aspects of Alzheimer disease (AD). Chromosome 21 contains several genes that have been implicated in neurodegenerative mechanisms. These include Cu/Zn superoxide dismutase (SOD-1), Ets-2 transcription factors, Down Syndrome Critical Region 1 (DSCR1) stress-inducible factor, and the amyloid precursor protein (APP). The accumulation of Abeta plaques is progressive across the lifespan in DS. Overexpression of APP in the obligate region for DS is associated with abundant Abeta plaques and tangles consistent with Braak stage V-VI. Intraneuronal Abeta in DS appears to trigger a pathological cascade leading to oxidative stress and a neurodegeneration typical of AD. There are suggestions that an increase in subcellular processing of APP and factors related to membrane APP cleavage favor the secretion of Abeta with age in DS. A misbalance between SOD-1 and glutathione perioxidase activity in DS has been linked to free radical generation. Ets-2 and DSCR1 overexpression in DS has been linked to cell degeneration. Age-related accumulation of somatic DNA mutations in both DS and AD contribute to oxidative stress that exacerbates the imbalance in gene expression. This leads to enhanced Abeta deposition and further neuronal vulnerability. The consequence of these factors and their temporal relationships is likely to be the subject of future research. Since the pathological processes leading to AD are seen across the lifespan in DS, an opportunity is afforded for early pharmacological intervention in the disorder.

Age Factors↗
PubMed2004

The short -term effects of an exercise programme as an adjunct to an orthosis in neuromuscular scoliosis.

The purpose of this study was to investigate the effects of a 4 week physiotherapy programme on patients who were given a spinal orthosis for neuromuscular scoliosis. This study was planned as a single group pre- and post-intervention repeated measures design. All patients were given a polyethylene spinal orthosis with an anterior opening. Fifteen (15) patients with neuromuscular diseases and a mean age of 12.46 years were evaluated. An exercises programme consisting of postural training, muscle strengthening and stretching exercises with special emphasis on respiratory exercises was given as an adjunct to orthotic treatment. The degree of impairment in forced vital capacity was 17.56% upon wearing an orthosis, it decreased to 9.28% following therapy (p < 0.05). There was also a statistically significant increase in muscle strength, balance duration and a significant decrease in limitation of range of motion. The results of the study imply that the conservative treatment of neuromuscular scoliosis should include an exercise programme as an adjunct to an orthosis, both to reduce the compromising effect of an orthosis on respiratory function and to support the patient's physical capacities.

Adolescent↗
PubMed2007

Autophagy genes protect against disease caused by polyglutamine expansion proteins in Caenorhabditis elegans.

Expanded polyglutamine (polyQ) proteins aggregate intracellularly in Huntington's disease and other neurodegenerative disorders. The lysosomal degradation pathway, autophagy, is known to promote clearance of polyQ protein aggregates in cultured cells. Moreover, basal autophagy in neuronal cells in mice prevents neurodegeneration by suppressing the accumulation of abnormal intracellular proteins. However, it is not yet known whether autophagy genes play a role in vivo in protecting against disease caused by mutant aggregate-prone, expanded polyQ proteins. To examine this question, we used two models of polyQ-induced toxicity in C. elegans, including the expression of polyQ40 aggregates in muscle and the expression of a human huntingtin disease fragment containing a polyQ tract of 150 residues (Htn-Q150) in ASH sensory neurons. Here, we show that genetic inactivation of autophagy genes accelerates the accumulation of polyQ40 aggregates in C. elegans muscle cells and exacerbates polyQ40-induced muscle dysfunction. Autophagy gene inactivation also increases the accumulation of Htn-Q150 aggregates in C. elegans ASH sensory neurons and results in enhanced neurodegeneration. These data provide in vivo genetic evidence that autophagy genes suppress the accumulation of polyQ aggregates and protect cells from disease caused by polyQ toxicity.

Animals↗
PubMed2001

Cytoplasmic domain mutations of the L1 cell adhesion molecule reduce L1-ankyrin interactions.

The neural adhesion molecule L1 mediates the axon outgrowth, adhesion, and fasciculation that are necessary for proper development of synaptic connections. L1 gene mutations are present in humans with the X-linked mental retardation syndrome CRASH (corpus callosum hypoplasia, retardation, aphasia, spastic paraplegia, hydrocephalus). Three missense mutations associated with CRASH syndrome reside in the cytoplasmic domain of L1, which contains a highly conserved binding region for the cytoskeletal protein ankyrin. In a cellular ankyrin recruitment assay that uses transfected human embryonic kidney (HEK) 293 cells, two of the pathologic mutations located within the conserved SFIGQY sequence (S1224L and Y1229H) strikingly reduced the ability of L1 to recruit 270 kDa ankyrinG protein that was tagged with green fluorescent protein (ankyrin-GFP) to the plasma membrane. In contrast, the L1 missense mutation S1194L and an L1 isoform lacking the neuron-specific sequence RSLE in the cytoplasmic domain were as effective as RSLE-containing neuronal L1 in the recruitment of ankyrin-GFP. Ankyrin binding by L1 was independent of cell-cell interactions. Receptor-mediated endocytosis of L1 regulates intracellular signal transduction, which is necessary for neurite outgrowth. In rat B35 neuroblastoma cell lines stably expressing L1 missense mutants, antibody-induced endocytosis was unaffected by S1224L or S1194L mutations but appeared to be enhanced by the Y1229H mutation. These results suggested a critical role for tyrosine residue 1229 in the regulation of L1 endocytosis. In conclusion, specific mutations within key residues of the cytoplasmic domain of L1 (Ser(1224), Tyr(1229)) destabilize normal L1-ankyrin interactions and may influence L1 endocytosis to contribute to the mechanism of neuronal dysfunction in human X-linked mental retardation.

Animals↗
PubMed2001

Neurodegenerative diseases.

This article briefly discusses and illustrates the major important neurodegenerative diseases of adulthood and neurometabolic (neurodegenerative in a broader sense) diseases of childhood and their gross neuropathology. Macroscopic views of the brain including the cerebellum and the brain stem and the spinal cord are given by external inspection as well as gross sections after brain cutting. Histologic details and photographs are supplied to explain and corroborate certain gross findings. This article attempts to correlate nosologic and neuropathologic features as the basis for interpreting neuroimaging data.

Adult↗
PubMed2001

A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion.

Huntington's disease (HD) is an autosomal dominant disorder characterized by abnormalities of movement, cognition, and emotion and selective atrophy of the striatum and cerebral cortex. While the etiology of HD is known to be a CAG trinucleotide repeat expansion, the pathways by which this mutation causes HD pathology remain unclear. We now report a large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movement, psychiatric symptoms, weight loss, dementia, and a relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal to ventral gradient and occasional intranuclear inclusions. All tested affected individuals, and no tested unaffecteds, have a CAG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation is novel. Cloning the causative CAG expansion mutation for this new disease, which we have termed Huntington's disease-like 2, may yield valuable insight into the pathogenesis of HD and related disorders.

Adult↗
PubMed2002

Infantile isolated sulphite oxidase deficiency in a Chinese family: a rare neurodegenerative disorder.

We report the clinical, biochemical, neuroradiological, and neurophysiological findings of a 4-year-old Chinese girl with infantile isolated sulphite oxidase deficiency. This is the first reported case in our locality. She presented at the age of 5 months with refractory seizures and developmental regression, and progressed rapidly to profound psychomotor retardation, spasticity, dystonia, microcephaly, and blindness. At the age of 3.5 years, she was admitted to the intensive care unit with septic shock. Ophthalmologic examination at this time revealed bilateral dislocation of the lens. Diagnosis of this very rare disorder was made on the basis of increased levels of urinary sulphite, thiosulphate, and sulphocysteine; normal urine xanthine and hypoxanthine; normal plasma uric acid; and low plasma cystine levels. The diagnosis was confirmed by the absence of sulphite oxidase activities in skin fibroblasts. Isolated sulphite oxidase deficiency is a rare inborn error of sulphur metabolism that is difficult to diagnose on clinical features and routine metabolic tests. The presence of ectopia lentis, seizures, and progressive neurological abnormalities should alert clinicians to the diagnosis.

Amino Acid Metabolism, Inborn Errors↗
PubMed2002

[Syndromes and diseases caused by mutations of trinucleotide expansions].

A novel type of mutation--due to expansion of DNA trinucleotide repeats--has been discovered about 10 years ago. Nowadays 15 genetic syndromes and diseases caused by these mutations are known such as FRA X A syndrome, FRA X E syndrome, Kennedy syndrome spinobulbare muscle atrophy, Curschmann-Steinert syndrome of myotonic dystrophia, Huntington disease, Friedreich ataxia, spinocerebellare ataxias types I., II., III., VI., VII., VIII., XII. and Taylor's oculopharyngeal muscle dystrophy. The mutations of instable trinucleotids represent some exceptions from the regular monogenic transmission such as premutation, genomic imprinting, generation anticipation (acceleration, accentuation), somatic mosaicism. A good understanding of their special properties is necessary for efficient interdisciplinar collaboration of medical teams taking care for these patients and their families.

Abnormalities, Multiple↗
PubMed2002

[Repair].

Transplantation of fetal neural cells represents an attractive replacement strategy for the treatment of certain neurodegenerative diseases. This is the case with Parkinson's disease, which results from a selective loss of dopaminergic neurons of the substantia nigra. Experimentation with animal models has demonstrated the feasibility of this approach. Grafting studies in patients have shown that intrastriatal implantation of solid grafts or cells obtained from human fetal mesencephalon usually results in a clinical benefit in patients. Despite continuous methodological progress, transplantation requires both conceptual and technical improvements. Current research aims at preventing the extensive death of donor dopaminergic neurons during the grafting procedure. However, the possibility of new sources of cells is currently being investigated. These include xenogeneic porcine neurons, or human cells programmed to produce dopamine or neurotrophic factors. A promising approach is based on the use of pluripotent stem cells derived from the brain, the bone marrow or early embryos. It is hoped that it will be possible to tightly control their proliferation and differentiation into dopaminergic neurons. Hence, it seems possible that transplantation will be widely used in the clinic in the future.

Animals↗