Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 60-year-old man with a 6-year history of tremor in his hands. He noted the onset of short of breath and gait disturbance in 1994; both of these symptoms were slowly progressive. Then recently he developed fever two months prior to the present admission. He was admitted to the rheumatology department of our hospital and neurological consultation was asked on December 13, 2000. On neurologic examination, he showed Gottron sign and fine crackle in both lungs. Pertinent neurological findings were bilateral dysmetria in finger-to-nose and heel-to-knee tests and a broad-based gait. In addition, he showed intention tremor in upper extremities more on the left. Romberg sign was positive. Deep tendon reflexes were decreased. Vibratory sensation was reduced at the wrists. The patient's hemoglobin was 11.1 g/dl, with a mean corpuscular volume of 92.0 fl. Vitamin B12 level was 190 (reference range, >230 pg/ml). Serum lactic acid, pyruvic acid and ceruloplasmin were slightly elevated. Chest X-ray showed interstitial pneumonia. Muscle biopsy showed grouping of small angular fiber. Brain MRI showed diffuse atrophy of the cerebral cortex and the cerebellum hemisphere. Thalamotomy did not improve his tremor. He was admitted again in November 2001. General worsening of his neurological findings was observed. IL2-receptor was markedly elevated. Serum anti-Hu, Yo and Ri antibodies were negative. An anaplastic carcinoma was found in his jejunum. He died from respiratory failure in February 2002. He was discussed in a neurological CPC and the chief discussant arrived at a conclusion that the patient had paraneoplastic syndrome. Other diagnosis entertained included MERRF, GSS, Ramsay Hunt syndrome, subacute combined degeneration, spinocerebellar degeneration. Majority of the participants thought that paraneoplastic syndrome was most likely. Post-mortem examination revealed poorly differentiated carcinoma in the small intestine. Myeline pallor was noted in the posterior and the lateral columns in the thoracic spine. Neuronal cell loss was observed in the Purkinje cell and granular cell layer in the cerebellum. Sural nerve demonstrated loss of myelinated fibers and grouping of small fibers. Neuropathological findings were consistent with Friedreich ataxia; nevertheless, no mutation was reported in frataxin in Japan. The neuropathologist concluded that neuropathological diagnosis was a spinocerebellar ataxia with neuropathological similarities to Friedreich ataxia.
 ...
PMID:[A 60-year-old man with intention tremor as an initial symptom followed by cerebellar ataxia, peripheral neuropathy and dementia]. 1614 16

The microtubule-associated protein tau has risk alleles for both Alzheimer's disease and Parkinson's disease and mutations that cause brain degenerative diseases termed tauopathies. Aggregated tau forms neurofibrillary tangles in these pathologies, but little is certain about the function of tau or its mode of involvement in pathogenesis. Neuronal iron accumulation has been observed pathologically in the cortex in Alzheimer's disease, the substantia nigra (SN) in Parkinson's disease and various brain regions in the tauopathies. Here we report that tau-knockout mice develop age-dependent brain atrophy, iron accumulation and SN neuronal loss, with concomitant cognitive deficits and parkinsonism. These changes are prevented by oral treatment with a moderate iron chelator, clioquinol. Amyloid precursor protein (APP) ferroxidase activity couples with surface ferroportin to export iron, but its activity is inhibited in Alzheimer's disease, thereby causing neuronal iron accumulation. In primary neuronal culture, we found loss of tau also causes iron retention, by decreasing surface trafficking of APP. Soluble tau levels fall in affected brain regions in Alzheimer's disease and tauopathies, and we found a similar decrease of soluble tau in the SN in both Parkinson's disease and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model. These data suggest that the loss of soluble tau could contribute to toxic neuronal iron accumulation in Alzheimer's disease, Parkinson's disease and tauopathies, and that it can be rescued pharmacologically.
 ...
PMID:Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. 2356 42

Objective. To verify whether systemic biometals dysfunctions affect neurotransmission in living Alzheimer's disease (AD) patients. Methods. We performed a case-control study using magnetoencephalography to detect sensorimotor fields of AD patients, at rest and during median nerve stimulation. We analyzed position and amount of neurons synchronously activated by the stimulation in both hemispheres to investigate the capability of the primary somatosensory cortex to reorganize its circuitry disrupted by the disease. We also assessed systemic levels of copper, ceruloplasmin, non-Cp copper (i.e., copper not bound to ceruloplasmin), peroxides, transferrin, and total antioxidant capacity. Results. Patients' sensorimotor generators appeared spatially shifted, despite no change of latency and strength, while spontaneous activity sources appeared unchanged. Neuronal reorganization was greater in moderately ill patients, while delta activity increased in severe patients. Non-Cp copper was the only biological variable appearing to be associated with patient sensorimotor transmission. Conclusions. Our data strengthen the notion that non-Cp copper, not copper in general, affects neuronal activity in AD. Significance. High plasticity in the disease early stages in regions controlling more commonly used body parts strengthens the notion that physical and cognitive activities are protective factors against progression of dementia.
...
PMID:Sensorimotor Cortex Reorganization in Alzheimer's Disease and Metal Dysfunction: A MEG Study. 2441 15

Aceruloplasminemia is characterized by progressive neurodegeneration with brain iron accumulation due to the complete lack of ceruloplasmin ferroxidase activity caused by mutations in the ceruloplasmin gene. Redox-active iron accumulation was found to be more prominent in the astrocytes than in the neurons. The most characteristic findings were abnormal or deformed astrocytes and globular structures of astrocytes. The lack of ceruloplasmin may primarily damage astrocytes in the aceruloplasminemic brains as a result of lipid peroxidation due to massive iron deposition. In the normal brain, iron may be continuously recycled between astrocytes and neurons, with transferrin acting as a shuttle. The glycosylphosphatidylinositol (GPI)-linked ceruloplasmin on astrocytes functions as a ferroxidase, mediating the oxidation of ferrous iron transported from the cytosol by ferroportin and its subsequent transfer to transferrin. In cases with aceruloplasminemia, neurons take up the iron from alternative sources of non-transferrin-bound iron, because astrocytes without GPI-linked ceruloplasmin cannot transport iron to transferrin. The excess iron in astrocytes could result in oxidative damage to these cells, and the neuronal cell protection offered by astrocytes would thus be disrupted. Neuronal cell loss may result from iron starvation in the early stage and from iron-mediated oxidation in the late stage. Ceruloplasmin may therefore play an essential role in neuronal survival in the central nervous system.
 ...
PMID:Aceruloplasminemia. 2516 55