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The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially(More)
A comprehensive, unbiased inventory of synuclein forms present in Lewy bodies from patients with dementia with Lewy bodies was carried out using two-dimensional immunoblot analysis, novel sandwich enzyme-linked immunosorbent assays with modification-specific synuclein antibodies, and mass spectroscopy. The predominant modification of alpha-synuclein in Lewy(More)
Galanin (GA) is a recently described neuropeptide that has been demonstrated to be widely distributed in the hypothalamus of experimental animals. So far there is no immunohistochemical description of GA in the human hypothalamus and, in particular, no studies of the colocalization of this neuropeptide with other transmitter candidates in the human(More)
Mutations in alpha-synuclein (alpha S) and parkin cause heritable forms of Parkinson disease (PD). We hypothesized that neuronal parkin, a known E3 ubiquitin ligase, facilitates the formation of Lewy bodies (LBs), a pathological hallmark of PD. Here, we report that affinity-purified parkin antibodies labeled classical LBs in substantia nigra sections from(More)
Increasing evidence suggests that phosphorylation may play an important role in the oligomerization, fibrillogenesis, Lewy body (LB) formation, and neurotoxicity of alpha-synuclein (alpha-syn) in Parkinson disease. Herein we demonstrate that alpha-syn is phosphorylated at S87 in vivo and within LBs. The levels of S87-P are increased in brains of transgenic(More)
Intracellular inclusions containing alpha-synuclein (alpha SN) are pathognomonic features of several neurodegenerative disorders. Inclusions occur in oligodendrocytes in multiple system atrophy (MSA) and in neurons in dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In order to identify disease-associated changes of alpha SN, this study(More)
Lewy bodies and coarse Lewy neurites are the pathological hallmarks of degenerating neurons in the brains of patients suffering from Parkinson's disease (PD). Recently, the presynaptic protein alpha-synuclein was shown to be a major component of Lewy bodies and Lewy neurites. This study demonstrates for the first time that extensive and thin(More)
We report on a pedigree of dominantly-inherited, adult-onset Alexander disease caused by the glial fibrillary acidic protein (GFAP) gene mutation, R416W. This pedigree highlights the importance of genetic analysis of the GFAP gene in leukodystrophy with palatal tremor.
Parkinson's disease (PD) is a neurodegenerative disease resulting from progressive loss of dopaminergic nigrostriatal neurons. α-Synuclein protein conformational changes, resulting in cytotoxic/aggregated proteins, have been linked to PD pathogenesis. We investigated a unilateral rotenone-lesioned mouse PD model. Unilateral lesion of the medial forebrain(More)
Characteristic ubiquitin-positive, tau-negative, degenerating neurites were present in brainstem regions known to be involved in idiopathic Parkinson's disease. Corresponding changes were entirely absent from controls and from the brainstems obtained from patients who had died with Alzheimer's disease, motor neuron disease and multiple system atrophy. In(More)