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a b s t r a c tIt is now well established, at least in animal models, that exercise elicits potent pro-cognitive and proneurogenic effects. Alzheimer's disease (AD) is one of the leading causes of dementia and represents one of the greatest burdens on healthcare systems worldwide, with no effective treatment for the disease to date. Exercise presents a promising non-pharmacological option to potentially delay the onset of or slow down the progression of AD. Exercise interventions in mouse models of AD have been explored and have been found to reduce amyloid pathology and improve cognitive function. More recent studies have expanded the research question by investigating potential pro-neurogenic and anti-inflammatory effects of exercise. In this review we summarise studies that have examined exercise-mediated effects on AD pathology, cognitive function, hippocampal neurogenesis and neuroinflammation in transgenic mouse models of AD. Furthermore, we attempt to identify the optimum exercise conditions required to elicit the greatest benefits, taking into account age and pathology of the model, as well as type and duration of exercise.© 2016 Elsevier B.V. All rights reserved. Please cite this article in press as: Ryan, S.M., Kelly, Á.M., Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer's disease. Ageing Res. Rev. (2016), http://dx

Helminths (worms) are one of the most successful organisms in nature given their ability to infect millions of humans and animals worldwide. Their success can be attributed to their ability to modulate the host immune response for their own benefit by releasing excretory-secretory (ES) products. Accordingly, ES products have been lauded as a potential source of immunomodulators/biotherapeutics for an array of inflammatory diseases. However, there is a significant lack of knowledge regarding the specific interactions between these products and cells of the immune response. Many different compounds have been identified within the helminth “secretome,” including antioxidants, proteases, mucin-like peptides, as well as helminth defense molecules (HDMs), each with unique influences on the host inflammatory response. HDMs are a conserved group of proteins initially discovered in the secretome of the liver fluke, Fasciola hepatica . HDMs interact with cell membranes without cytotoxic effects and do not exert antimicrobial activity, suggesting that these peptides evolved specifically for immunomodulatory purposes. A peptide generated from the HDM sequence, termed FhHDM-1, has shown extensive anti-inflammatory abilities in clinically relevant models of diseases such as diabetes, multiple sclerosis, asthma, and acute lung injury, offering hope for the development of a new class of therapeutics. In this review, the current knowledge of host immunomodulation by a range of F. hepatica ES products, particularly FhHDM-1, will be discussed. Immune regulators, including HDMs, have been identified from other helminths and will also be outlined to broaden our understanding of the variety of effects these potent molecules exert on immune cells.