Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication. | ||||||||
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Nurr1 in Parkinson's disease and related disorders.Chu Y, Le W, Kompoliti K, Jankovic J, Mufson EJ, Kordower JH Department of Neurological Science, Rush University Medical Center, Chicago, Illinois 60612, USA. In mammals, the transcription factor Nurr1 is expressed early in development and continues to be detectable throughout the organism's lifetime. Nurr1 is involved in the establishment and maintenance of the dopaminergic phenotype within specific central nervous system neuronal subpopulations including the nigrostriatal dopamine system. This protein is reduced over the course of normal aging, which is a major risk factor for Parkinson's disease (PD). However, whether Nurr1 expression is affected by PD has not been documented. The present study examined the role of Nurr1 in the maintenance of the dopaminergic phenotype within neurons in substantia nigra in PD compared with patients with diagnoses of progressive supranuclear palsy (PSP) or Alzheimer's disease (AD) or age-matched-matched controls. In PD, the optical density (OD) of Nurr1 immunofluorescence was significantly decreased in nigral neurons containing alpha-synuclein-immunoreactive inclusions. Similarly, the OD of Nurr1 immunofluorescence intensity in the nigra of AD cases was decreased in neurons with neurofibrillary tangles (NFTs). In contrast to PD and AD, the OD of Nurr1 immunofluorescence intensity was severely decreased in the neurons with or without NFTs in PSP cases. Decline of Nurr1-ir neuronal number and OD was observed within substantia nigra (SN) neurons in PD but not within hippocampal neurons. The decline in Nurr1-ir expression was correlated with loss of tyrosine hydroxylase immunofluorescence across the four groups. These data demonstrate that Nurr1 deficiency in dopaminergic neurons is associated with the intracellular pathology in both synucleinopathies and tauopathies. Published 6 December 2005 in J Comp Neurol, 494(3): 495-514.
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