Santos Guido, Díaz Mario, Torres Néstor V
Systems Biology and Mathematical Modelling Group, Departamento de Bioquímica, Microbiología, Biología Celular y Genética, Instituto de Tecnologías Biomédicas, CIBICAN, Universidad de La Laguna San Cristóbal de La Laguna, Spain.
Laboratorio de Fisiología y Biofísica de Membranas, Departamento de Biología Animal y Edafología y Geología, Facultad de Ciencias, Unidad Asociada de Investigación ULL-CSIC, Universidad de La Laguna San Cristóbal de La Laguna, Spain.
Front Physiol. 2016 Mar 15;7:90. doi: 10.3389/fphys.2016.00090. eCollection 2016.
A connection between lipid rafts and Alzheimer's disease has been studied during the last decades. Mathematical modeling approaches have recently been used to correlate the effects of lipid composition changes in the physicochemical properties of raft-like membranes. Here we propose an agent based model to assess the effect of lipid changes in lipid rafts on the evolution and progression of Alzheimer's disease using lipid profile data obtained in an established model of familial Alzheimer's disease. We have observed that lipid raft size and lipid mobility in non-raft domains are two main factors that increase during age and are accelerated in the transgenic Alzheimer's disease mouse model. The consequences of these changes are discussed in the context of neurotoxic amyloid β production. Our agent based model predicts that increasing sterols (mainly cholesterol) and long-chain polyunsaturated fatty acids (LCPUFA) (mainly DHA, docosahexaenoic acid) proportions in the membrane composition might delay the onset and progression of the disease.
在过去几十年中，人们一直在研究脂筏与阿尔茨海默病之间的联系。最近，数学建模方法已被用于关联脂筏样膜的脂质组成变化对其物理化学性质的影响。在此，我们提出一种基于主体的模型，利用在家族性阿尔茨海默病既定模型中获得的脂质谱数据，评估脂筏中脂质变化对阿尔茨海默病演变和进展的影响。我们观察到，非脂筏区域的脂筏大小和脂质流动性是随年龄增长而增加且在转基因阿尔茨海默病小鼠模型中加速的两个主要因素。这些变化的后果在神经毒性淀粉样β蛋白产生的背景下进行了讨论。我们基于主体的模型预测，增加膜组成中固醇（主要是胆固醇）和长链多不饱和脂肪酸（LCPUFA）（主要是DHA，二十二碳六烯酸）的比例可能会延迟疾病的发作和进展。
