Inhibition of Glycolysis as a Treatment for Neurodegeneration

Researchers here discuss a program of drug discovery that led to inhibitors of glycolysis as a potential approach to treatment for neurodegenerative conditions. The researchers note that elevated glycolysis is a characteristic of Alzheimer's disease, for example. There are always many, many mechanisms and altered aspects of cell metabolism one can investigate in aging and age-related disease. The question to ask when looking at any one specific mechanism in isolation is how much of the pathology of the condition lies downstream of this mechanism. It is all to easy to find oneself targeting a side-effect, or a minor mechanism that is not close to the root causes of the condition, which is why it is important to test in animals to observe the degree to which health is improved. Although it is widely agreed that proteotoxicity drives impairments in Alzheimer's disease (AD) and other neurological diseases, many preclinical and case-report studies indicate that increased microglial production of pro-inflammatory cytokines such as TNF-a mediate proteotoxicity in AD and other neurological conditions. We developed parallel high-throughput phenotypic screens to discover small molecules which inhibit age-related proteotoxicity in a C. elegans model of AD, and microglia inflammation (LPS-induced TNF-a). In the initial screen of 2,560 compounds, the most protective compounds were, in order, phenylbutyrate (HDAC inhibitor), methicillin (beta lactam antibiotic), and quetiapine (tr...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs