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Mechanistic interpretations in these studies typically rely on indirect evidence, such as changes in protein markers (e.g., Bax/Bcl-2 ratio, caspase activity), while direct causal validationthrough gene silencing, overexpression, or target binding assaysis rare (Xu G

J Cereb Blood Flow Metab 32:502514 Ppin J, Francelle L, Carrillo-de Sauvage MA, de Longprez L, Gipchtein P, Cambon K, Valette J, Brouillet E, Flament J (2016) In vivo imaging of brain glutamate defects in a knock-in mouse model of Huntingtons disease

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Mice lacking apoA-I develop autoimmunity when challenged with a high cholesterol (diet and background, Ldlr -/- ), which includes T cell activation and production of autoantibodies (821,822)

Stark M, Wichman C, Avivi I, Assaraf YG

While this line of investigation continues, it hasnt yet generated the same level of reproducible data seen in metabolic research