DJ-1 knock-down in astrocytes impairs astrocyte-mediated neuroprotection against rotenone

NEUROBIOLOGY OF DISEASE

卷:33

Article

Mullett, Steven J. ; Hinkle, David A.

关键词: Astrocyte;    Glia;    Parkinson's disease;    DJ-1;    siRNA;    Rotenone;    Neuroprotection;    PARK7;   

DOI  :  10.1016/j.nbd.2008.09.013

来源: Elsevier

【 摘 要 】

Mutations that eliminate DJ-1 expression cause a familial form of Parkinson's disease (PD). In sporadic PD, and many other neurodegenerative diseases, reactive astrocytes over-express DJ-1 whereas neurons maintain its expression at non-disease levels. Since DJ-1 has neuroprotective properties, and since astrocytes are known to support and protect neurons, DJ-1 over-expression in reactive astrocytes may reflect an attempt by these cells to protect themselves and surrounding neurons against disease progression. We used neuron-astrocyte contact and non-contact co-cultures to show that DJ-1 knock-down in astrocytes impaired their neuroprotective capacity, relative to wild-type astrocytes, against the neurotoxin rotenone. Conversely, DJ-1 over-expression in astrocytes augmented their neuroprotective capacity. Experiments using astrocyte conditioned media on neuron-only cultures suggested that astrocyte-released, soluble factors were involved in the DJ-1-dependent, astrocyte-mediated neuroprotective mechanism. Our findings support the developing view that astrocytic dysfunction, in addition to neuronal dysfunction, may contribute to the progression of a variety of neurodegenerative disorders. (c) 2008 Elsevier Inc. All rights reserved.

【 授权许可】

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