Marine bacterial extracts as a new rich source of drugs against Alzheimer's disease

Alzheimer's disease (AD) is a prevalent, progressive and irreversible, neurodegenerative disease with no disease modifying treatment yet available. The projected burden of AD on our healthcare system is immense and thus there is an immediate need for new drugs that prevent or attenuate AD symptoms. While most efforts in the field are directed at treatments that reduce amyloid or tau burden in the brain, we have taken an alternate approach - a model based on reducing AD-associated neuronal cell cycle events. Using this model, we have screened a largely unexplored source of compounds with therapeutic potential - the natural products created by diverse strains of marine bacteria. Two hundred and twenty-five bacterial extracts from different strains were tested for both toxicity and neuroprotective properties by crystal violet and In-cell Western - first in HT22 cells and then in mouse primary neuronal cultures. Based on these screens, we have identified several promising leads, and here we focus on the most promising of these. We found that we could directly assay even a crude bacterial extract in our E16 mouse cortical neuronal cultures and screen for activities that prevent cell cycle reentry and preserve synaptic structure. Preliminary tests in 1-month-old animals from a mouse model of Ataxia telangiectasia, showed that blockage of cell cycle-related neuronal death could also be successful in vivo. This adds an important extension to our in vitro studies. These findings showcase a new effective and efficient assay system and validate the use of marine natural compounds as a novel source for new drugs to fight Alzheimer's disease. Cover Image for this issue: doi: 10.1111/jnc.14733.