Apoptosis-inducing factor mediates dopaminergic cell death in response to LPS-induced inflammatory stimulus Evidence in Parkinson's disease patients

作者：Burguillos M A; Hajji N; Englund E; Persson A; Cenci A M; Machado A; Cano J; Joseph B; Venero J L^*

来源：Neurobiology of Disease, 2011, 41(1): 177-188.

DOI：10.1016/j.nbd.2010.09.005

• Apoptosis-inducing factor
• Caspase 3
• Apoptosis
• Parkinson's disease
• Substantia nigra
• Dopamine

We show that intranigral lipopolysaccharide (LPS) injection, which provokes specific degeneration of DA neurons, induced caspase-3 activation in the rat ventral mesencephalon, which was mostly associated with glial cells. In contrast, nigral DA neurons exhibited AIF nuclear translocation in response to LPS. A significant decrease of the Bcl-2/Bax ratio in nigral tissue after LPS injection was observed. We next developed an in vitro co-culture system with the microglial BV2 and the DA neuronal MN9D murine cell lines. The silencing of caspase-3 or AIF by small interfering RNAs exclusively in the DA MN9D cells demonstrated the key role of AIF in the LPS-induced death of DA cells. In vivo chemical inhibition of caspases and poly(ADP-ribose) polymerase-1, an upstream regulator of AIF release and calpain, proved the central role of the AIF-dependent pathway in LPS-induced nigral DA cell death. We also observed nuclear translocation of AIF in the ventral mesencephalon of Parkinson's disease subjects. CO 2010 Elsevier Inc.

• 出版日期2011-1