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Mutations of the parkin gene are the most frequent cause of early onset autosomal recessive parkinsonism (EO-AR). Here we show that inactivation of the parkin gene in mice results in motor and cognitive deficits, inhibition of amphetamine-induced dopamine release and inhibition of glutamate neurotransmission. The levels of dopamine are increased in the(More)
Tau-containing filaments purified from the brain of progressive supranuclear palsy (PSP) patients were isolated and characterized. These filaments co-purify with regular particles that biophysical and biochemical methods identified as ferritin shells. In vivo, brain tau accumulation in PSP co-localized with ferritin. These results suggest that ferritin/iron(More)
Parkinson's disease is a neurodegenerative disorder which is in most cases of unknown etiology. Mutations of the Park-2 gene are the most frequent cause of familial parkinsonism and parkin knockout (PK-KO) mice have abnormalities that resemble the clinical syndrome. We investigated the interaction of genetic and environmental factors, treating midbrain(More)
Progressive supranuclear palsy (PSP) is a mostly sporadic disorder of unknown pathogenesis. Familial PSP have been reported related to mutations of microtubule-associated protein tau (MAPT). Mutations of the Park2 gene cause autosomal recessive parkinsonism with neuropathological findings consistent with neurofibrillary tangles and tau immunoreactive(More)
Tauopathies are neurodegenerative diseases, sporadic or familial, mainly characterized by dementia and parkinsonism associated to atrophy of the frontotemporal cortex and the basal ganglia, with deposition of abnormal tau in brain. Hereditary tauopathies are related with mutations of the tau gene. Up to the present, these diseases have not been helped by(More)
The role of glia in Parkinson's disease (PD) is very interesting because it may open new therapeutic strategies in this disease. Traditionally it has been considered that astrocytes and microglia play different roles in PD: Astroglia are considered the "good" glia and have traditionally been supposed to be neuroprotective due to their capacity to quench(More)
Parkin mutations in humans produce parkinsonism whose pathogenesis is related to impaired protein degradation, increased free radicals, and abnormal neurotransmitter release. The role of glia in parkin deficiency is little known. We cultured midbrain glia from wild-type (WT) and parkin knock-out (PK-KO) mice. After 18-20 d in vitro, PK-KO glial cultures had(More)
L-DOPA kills dopamine neurones in culture but is the most effective drug for the treatment of Parkinson's disease, where it exhibits no clear toxicity. While glial cells surround and protect neurones in vivo, neurones are usually cultured in vitro in the absence of glia. We treated fetal midbrain rat neurones with L-DOPA, mesencephalic glia conditioned(More)
Parkin mutations in humans produce parkinsonism whose pathogenesis is related to impaired protein degradation, increased free radicals and abnormal neurotransmitter release. In this study, we have investigated whether partial proteasomal inhibition by epoxomicin, an ubiquitin proteasomal system (UPS) irreversible inhibitor, further aggravates the cellular(More)
In this work we investigate the role of CHIP in a new CHIP-mutation related ataxia and the therapeutic potential of trehalose. The patient's fibroblasts with a new form of hereditary ataxia, related to STUB1 gene (CHIP) mutations, and three age and sex-matched controls were treated with epoxomicin and trehalose. The effects on cell death, protein misfolding(More)