Justo García de Yébenes

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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)
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)
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)
l-DOPA is the most effective treatment for Parkinson's disease but in isolated neuronal cultures it is neurotoxic for dopamine (DA) neurones. Experiments in vivo and clinical studies have failed to show toxicity of l-DOPA in animals or patients but that does not exclude the possibility of a toxic effect of l-DOPA on patients with certain genetic risk(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)
Nitric oxide (NO) is a modulator of differentiation and survival of dopamine (DA) neurons. NO may play a role in the pathogenesis of Parkinson's disease (PD) since its levels are increased in parkinsonian brains and it can nitrosylate and alter the function of key proteins involved in the pathogenesis of PD. NO producing neurons are spared in parkinsonian(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)
We investigated the environmental and genetic factors for Alzheimer's disease (AD) in Spain and performed a door to door study of a cohort of more than 500 subjects, over 70 years old, from Leganés, a suburban area near Madrid. The cohort was followed for 6 years by neurologists and other health workers and was divided in three groups: normal controls,(More)
Steele-Richardson-Olszewski syndrome (SROS) is a neurodegenerative disorder of unknown aetiology, most frequently sporadic. Familial cases of SROS have been described. An intronic polymorphism of the tau gene is associated with sporadic SROS and mutations of the tau gene are present in atypical cases of SROS. The role of tau has been excluded in other(More)