Multi-scale Quantitative Assessment of Apoptosis, Bioenergetics, and Oxidative Stress Molecular Mechanisms in the SOD1 G93A Transgenic ALS Mouse Model
Zhang, Kenneth Y.
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Apoptosis, bioenergetics, and oxidative stress have been implicated in Amyotrophic Lateral Sclerosis (ALS) disease progression; it is unclear as to how the interactions within this highly inter-related triad of categories influences the time course of the disease or, how effective therapeutic modulation could be accomplished. In this multi-scale study, we aim to simulate the molecular responses in ALS and map the timing of the interactions between the response mechanisms in high-copy SOD1 G93A (superoxide dismutase-1, glycine 93 to alanine) transgenic mice in order to determine which parameters and relationships have the most significant impact on ALS in each stage of the pathology. In addition, the possibility of homeostatic instabilities within the triad prior to, during, and after ALS symptom onset is examined. We observed several apoptosis- and oxidative stress-related metrics which are elevated throughout ALS disease course, with evidence of early disturbances. We identify regulatory differences within the apoptosis-bioenergetics-oxidative stress triad between G93A and wild type mice that could contribute to homeostatic instability leading to ALS symptom onset and disease progression.