Amyotrophic SRT3109 inhibitor Lateral Sclerosis is the most common adultonset motor neuron disease, with a lifetime risk of 1 in 2000 and a worldwide incidence of 1�C3 new cases per 100,000 individuals. Symptoms of ALS include spasticity, hyperreflexia, generalized weakness, fasciculations, muscle atrophy, and paralysis resulting in impaired respiratory function. Ultimately, this leads to death within 3�C5 years of onset, most commonly from respiratory failure. The causes of ALS are poorly understood: only 10% of the cases are inherited, and only 20% of these cases have been definitively linked to mutations in the superoxide dismutase 1 gene. The majority of the cases are sporadic, and the causes are largely unknown. Regardless of the type of ALS, patients exhibit neuronal cell death, which may be caused by excess glutamate and oxidative stress-induced metabolic dysfunction. Pathological hallmarks of ALS include mitochondrial dysfunction, increased oxidative stress, glutamate excitotoxicity,, proteinopathy, glutaminergic dysregulation, metabolic dysregulation, and motor neuron death. These disrupted cellular functions represent discrete targets for therapies that may ameliorate disease progression. Evidence suggests that the histopathological and biochemical hallmarks of ALS result from impaired energy metabolism. Previous work reported by Zhao et al. has shown that a ketogenic diet or caprylic triglyceride stalls the impairment of motor function and reduces death of motor neurons in the spinal cord of transgenic ALS mice by restoring energy 10-Hydroxycamptothecin inhibitor metabolism through ketone body utilization. These transgenic ALS mice express mutant forms of the human SOD1 gene and multiple copies of the wild type human SOD1 gene; therefore, this mouse model is frequently used for studying the progression and mechanism of ALS pathogenesis. Under normal conditions, glucose is the primary metabolic fuel for the cells. However, alternative fuels such as ketone bodies or TCA cycle intermediates can potentially bypass the ratelimiting steps associated with impaired neuronal glucose metabolism and restore mitochondrial ATP production. Indeed, metabolic therapies such as therapeutic ketosis have been shown to effectively treat or alleviate symptoms of neurological disorders associated with aberrant energy metabolism, such as epilepsy, even in the presence of a persistent molecular pathology.