FABP7 upregulation induces a neurotoxic phenotype in astrocytes.
FABP7 upregulation induces a neurotoxic phenotype in astrocytes.
复制标题
作者：
Killoy KM;Harlan BA;Pehar M;Vargas MR
Fatty acid binding proteins (FABPs) are key regulators of lipid metabolism, energy homeostasis and inflammation. They participate in fatty acid metabolism by regulating their uptake, transport and availability of ligands to nuclear receptors. In the adult brain, FABP7 is especially abundant in astrocytes that are rich in cytoplasmic granules originated from damaged mitochondria. Mitochondrial dysfunction and oxidative stress have been implicated in the neurodegenerative process observed in amyotrophic lateral sclerosis (ALS), either as a primary cause or as a secondary component of the pathogenic process. Here we investigated the expression of FABP7 in animal models of human superoxide dismutase 1 (hSOD1)-linked ALS. In the spinal cord of symptomatic mutant hSOD1-expressing mice, FABP7 is up-regulated in gray matter astrocytes. Using a co-culture model, we examined the effect of increased FABP7 expression in astrocyte-motor neuron interaction. Our data shows that FABP7 over-expression directly promotes an NF-κB-driven pro-inflammatory response in non-transgenic astrocytes that ultimately is detrimental for motor neuron survival. Addition of trophic factors, capable of supporting motor neuron survival in pure cultures, did not prevent motor neuron loss in co-cultures with FABP7 over-expressing astrocytes. In addition, astrocyte cultures obtained from symptomatic hSOD1-expressing mice display up-regulated FABP7 expression. Silencing endogenous FABP7 in these cultures decreases the expression of inflammatory markers and their toxicity towards co-cultured motor neurons. Our results identify a key role of FABP7 in the regulation of the inflammatory response in astrocytes and identify FABP7 as a potential therapeutic target to prevent astrocyte-mediated motor neuron toxicity in ALS.
登录
查看更多内容
影响因子：
7.7
作者：
Garin-Shkolnik, Tali;Rudich, Assaf;Rubinstein, Menachem
通讯作者：
Rubinstein, Menachem
影响因子：
12.7
作者：
Ditsworth D;Maldonado M;McAlonis-Downes M;Sun S;Seelman A;Drenner K;Arnold E;Ling SC;Pizzo D;Ravits J;Cleveland DW;Da Cruz S
通讯作者：
Da Cruz S
影响因子：
4.8
作者：
Ellinghaus, P;Wolfrum, C;Seedorf, U
通讯作者：
Seedorf, U
影响因子：
64.5
作者：
Bailey AP;Koster G;Guillermier C;Hirst EM;MacRae JI;Lechene CP;Postle AD;Gould AP
通讯作者：
Gould AP
影响因子：
46.9
作者：
通讯作者：
--