Ward Roberta J, Dexter David T, Crichton Robert R
Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Imperial College, London UK,
Front Biosci (Schol Ed). 2015 Jun 1;7(1):189-204. doi: 10.2741/S433.
During ageing, different iron complexes accumulate in specific brain regions which are associated with motor and cognitive dysfunction. In neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, changes in local iron homoeostasis result in altered cellular iron distribution and accumulation, ultimately inducing neurotoxicity. The use of iron chelators which are able to penetrate the blood brain barrier and reduce excessive iron accumulation in specific brain regions have been shown to reduce disease progression in both Parkinson's disease and Friedreich's Ataxia. Neuroinflammation often occurs in neurodegenerative diseases, which is mainly sustained by activated microglia exhibiting the M1 phenotype. Such inflammation contributes to the disease progression. Therapeutic agents which reduce such inflammation, e.g. taurine compounds, may ameliorate the inflammatory process by switching the microglia from a M1 to a M2 phenotype.
在衰老过程中,不同的铁复合物在特定脑区积累,这些脑区与运动和认知功能障碍有关。在神经退行性疾病中,如阿尔茨海默病和帕金森病,局部铁稳态的变化导致细胞内铁分布和积累改变,最终诱发神经毒性。能够穿透血脑屏障并减少特定脑区过量铁积累的铁螯合剂已被证明可减缓帕金森病和弗里德赖希共济失调的疾病进展。神经炎症常发生在神经退行性疾病中,主要由表现为M1表型的活化小胶质细胞维持。这种炎症会促进疾病进展。减少这种炎症的治疗剂,如牛磺酸化合物,可能通过将小胶质细胞从M1表型转变为M2表型来改善炎症过程。