Neuroprotection in metabolism-based therapy

Abstract

Metabolism-based therapy has been used successfully in the treatment of seizures but study of its use in other neurodegenerative disorders is growing. Data demonstrating the use of different forms of metabolism-based therapy in human trials of Alzheimer disease and Parkinson disease are discussed. Animal and in vitro studies have shed light on metabolism-based therapy’s mechanisms in these diseases, as well as ALS, aging, ischemia, trauma and mitochondrial cytopathies. Additional insights may be obtained by considering the role of metabolism-based therapy in cell disability and death (specifically apoptosis, excitotoxicity, and autophagy).

The New Ketone Alphabet Soup: BHB, HCA, and HDAC

“…In a second study by Rahman and colleagues, and relevant to the neuroprotective effects of ketone bodies and KDs (11,12), a unique target mechanism was recently identified. Adipocytes typically release free fatty acids, but this process is prevented by BHB, acting via the HCA 2 (also known as NIACR1 or niacin receptor 1), a G protein-coupled receptor found on adipocytes, neutrophils, tissue macrophages, and in the anterior cingulate cortex (13,14).…”

Ketogenic diet and its impact on mental processes of working population

“…KD is efficient with ameliorating symptoms of AD, Parkinson's disease and other ND (Hartman, 2012, Liśkiewicz et al, 2012, Mandla et al, 2013. KD can have a profound effect on neuronal plasticity, reduces inflammation, and improves bioenergetics in the brain … (Procaccio et al, 2014).…”

Ketogenic Diet Attenuates NMDA-Induced Damage to Rat's Retinal Ganglion Cells in an Age-Dependent Manner

“…The KD (F3666 Ketogenic Diet for Rodents; Bio-Serv, Frenchtown, N.J., USA) consisted of 78.8% fats, 8.4% proteins, 5% cellulose, less than 5% water, and less than 1% carbohydrates, and was supplemented with necessary minerals and amino acids (detailed information available at supplier's http://www.bio-serv.com/pdf/F3666.pdf). The KD of this specific composition has been commonly used in pre-clinical research as its composition closely mimics that of the classic KD used clinically in patients [2,3]. To confirm the development of ketosis and hypoglycaemia in rats fed the KD, blood concentrations of β-hydroxybutyrate and glucose were measured in rats on day 14 of exposure to the KD and in the control rats for comparison using the Precision Xtra Blood Glucose and Ketone Monitoring System (Abbott, Alameda, Calif., USA) [12].…”

“…Although there are different variants of KDs, they all result in mimicking the biochemical changes that occur during starvation or extremely limited supply of carbohydrates with consequent changes in various metabolic and non-metabolic pathways related to energy metabolism, GABAergic inhibitory system, glutamatergic excitatory system, antioxidant mechanisms, programmed cell death, anti-inflammatory processes, and kynurenic acid production [2,3]. …”

“…Diets high in fats and low in carbohydrates and proteins (so-called ketogenic diets, KDs) are one emerging non-pharmacological approach to treat neurodegenerative processes in disorders such as brain trauma, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis [2,3]. Although there are different variants of KDs, they all result in mimicking the biochemical changes that occur during starvation or extremely limited supply of carbohydrates with consequent changes in various metabolic and non-metabolic pathways related to energy metabolism, GABAergic inhibitory system, glutamatergic excitatory system, antioxidant mechanisms, programmed cell death, anti-inflammatory processes, and kynurenic acid production [2,3].…”