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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pathological properties of the Parkinson's disease-associated protein DJ-1 in alpha-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick's disease.

Mutations in the PARK7 gene DJ-1 are associated with recessive hereditary Parkinson's disease (PD). Fibrillar inclusions of alpha-synuclein comprise the neuropathological hallmarks of PD and related Lewy body diseases as well as multiple system atrophy (MSA). Moreover, neuronal and glial inclusions containing tau have been observed in alpha-synucleinopathy patients. Using a collection of antibodies against DJ-1, we have performed a comprehensive investigation of DJ-1 in alpha-synucleinopathies and tauopathies. DJ-1 was abundantly expressed in reactive astrocytes of patients with neurodegenerative diseases. Likewise, DJ-1 antiserum immunostained reactive astrocytes that became abundant with disease progression in the brain stem of transgenic mice expressing mutant [A30P]alpha-synuclein. Human Lewy bodies as well as Lewy body-like inclusions in the alpha-synuclein transgenic mice were DJ-1 negative. Neuronal tau inclusions were DJ-1 immunopositive in Pick's disease (PiD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer's disease. In addition, we found DJ-1-immunopositive glial inclusions in CBD, PSP and MSA. Biochemical extraction experiments revealed the specific presence of insoluble, modified DJ-1 in PiD and MSA. Our results suggest that DJ-1 is up-regulated in reactive astrocytes as well as in neuronal and glial cells with specific alpha-synucleinopathy and tauopathy.[1]


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