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Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer’s disease

Acta Pharmaceutica Sinica B 2022年第2期12卷 511-531页

作者： Steven N.Austad Scott Ballinger thomas w.buford Christy S.Carter Daniel L.Smith Jr Victor Darley-Usmar Jianhua Zhang Department of Biology University of Alabama at BirminghamBirminghamAL 35294USA Department of Pathology University of Alabama at BirminghamBirminghamAL 35294USA Department of Medicine University of Alabama at BirminghamBirminghamAL 35294USA Department of Nutrition Sciences University of Alabama at BirminghamBirminghamAL 35294USA

Aging is by far the most prominent risk factor for Alzheimer’s disease(AD),and both aging and AD are associated with apparent metabolic *** developing effective therapeutic interventions to treat AD is clearly in urgent need,the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients,on disease pathogenesis,have been *** is also an increasing awareness of differential risk and potential targeting strategies related to biological sex,microbiome,and circadian *** a major part of intracellular metabolism,mitochondrial bioenergetics,mitochondrial quality-control mechanisms,and mitochondria-linked inflammatory responses have been considered for AD therapeutic *** review summarizes and highlights these efforts.

关键词： Mitochondrial DNA Mitochondrial electron transport chain Mitochondrial quality control Reactive species DAMPs Hexokinase biosynthesis pathway Diabetes Circadian regulation Microbiome

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Moose at their bioclimatic edge alter their behavior based on weather, landscape, and predators

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Current Zoology 2018年第4期64卷 419-432页

作者： Mark A. DITMER Ron A. MOEN Steve K. wINDELS James D. FORESTER thomas E, NESS Tara R. HARRIS Conservation Department Minnesota Zoo 13000 Zoo Boulevard Apple Valley MN 55124 USA Department of Fisheries Wildlife and Conservation Biology University of Minnesota 2003 Upper Buford Circle Ste 135 St Paul MN 55108 USA Natural Resources Research Institute and Department of Biology University of Minnesota Duluth 5013 Miller Trunk Highway Duluth MN 55811 USA Voyageurs National Park 360 Hwy 11 E International Falls MN 56649 USA

Populations inhabiting the bioclimatic edges of a species' geographic range face an increasing amount of stress from alterations to their environment associated with climate change. Moose are large-bodied ungulates that are sensitive to heat stress and have exhibited population declines and range contractions along their southern geographic extent. Using a hidden Markov model to analyze movement and accelerometer data, we assigned behaviors (rest, forage, or travel) to all locations of global positioning system-collared moose (13, moose-years = 19) living near the southern edge of the species' range in and around Voyageurs National Park, MN, USA. we assessed how moose behavior changed relative to weather, landscape, and the presence of predators. Moose significantly reduced travel and increased resting behaviors at ambient temperatures as low as 15 °C and 24 °C during the spring and summer, respectively. In general, moose behavior changed seasonally in association with distance to lakes and ponds. Moose used wetlands for travel throughout the year, rested in conifer forests, and foraged in shrublands. The influence of wolves varied among individual moose and season, but the largest influence was a reduction in travel during spring when near a wolf home range core, primarily by pregnant females. Our analysis goes beyond habitat selection to capture how moose alter their activities based on their environment. Our findings, along with climate change forecasts, suggest that moose in this area will be required to further alter their activity patterns and space use in order to find sufficient forage and avoid heat stress.

关键词：气候变化食肉动物驼鹿行为天气生物风景地理范围

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