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

Summary, in English

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.

• Författare: Miguel Burguillos Garcia; N Hajji; E Englund; A Persson; Angela Cenci Nilsson; A Machado; J Cano; B Joseph; J L Venero
• Avdelning/ar: Basala gangliernas patofysiologi; MultiPark: Multidisciplinary research focused on Parkinson´s disease
• Publiceringsår: 2011
• Språk: Engelska
• Sidor: 177-188
• Publikation/Tidskrift/Serie: Neurobiology of Disease
• Volym: 41
• Fulltext: - 13 MB; Download statistics
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/20850531?dopt=Abstract; http://dx.doi.org/10.1016/j.nbd.2010.09.005
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Neurosciences
• Status: Published
• Forskningsgrupp: Basal Ganglia Pathophysiology
• ISBN/ISSN/Övrigt: ISSN: 0969-9961