Pathological properties of the Parkinson’s disease-associated protein DJ-1 in α-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 α-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 α-synucleinopathy patients. Using a collection of antibodies against DJ-1, we have performed a comprehensive investigation of DJ-1 in α-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]α-synuclein. Human Lewy bodies as well as Lewy body-like inclusions in the α-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 α-synucleinopathy and tauopathy.

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