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It has been established that H<jats:sub>2<\/jats:sub>S homeostasis is balanced in AD. The emerging mitochondrial roles of H<jats:sub>2<\/jats:sub>S include antioxidation, antiapoptosis, and the modulation of cellular bioenergetics. Here, using primary neurons from the well\u2010characterized APP\/PS1 transgenic mouse model, we studied the effects of AP39 (a newly synthesized mitochondrially targeted H<jats:sub>2<\/jats:sub>S donor) on mitochondrial function. AP39 increased intracellular H<jats:sub>2<\/jats:sub>S levels, mainly in mitochondrial regions. AP39 exerted dose\u2010dependent effects on mitochondrial activity in APP\/PS1 neurons, including increased cellular bioenergy metabolism and cell viability at low concentrations (25\u2013100\u2009nM) and decreased energy production and cell viability at a high concentration (250\u2009nM). Furthermore, AP39 (100\u2009nM) increased ATP levels, protected mitochondrial DNA, and decreased ROS generation. AP39 regulated mitochondrial dynamics, shifting from fission toward fusion. After 6 weeks, AP39 administration to APP\/PS1 mice significantly ameliorated their spatial memory deficits in the Morris water maze and NORT and reduced A<jats:italic>\u03b2<\/jats:italic> deposition in their brains. Additionally, AP39 inhibited brain atrophy in APP\/PS1 mice. Based on these results, AP39 was proposed as a promising drug candidate for AD treatment, and its anti\u2010AD mechanism may involve protection against mitochondrial damage.<\/jats:p>","DOI":"10.1155\/2016\/8360738","type":"journal-article","created":{"date-parts":[[2016,1,31]],"date-time":"2016-01-31T21:05:15Z","timestamp":1454274315000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["AP39, a Mitochondria\u2010Targeted Hydrogen Sulfide Donor, Supports Cellular Bioenergetics and Protects against Alzheimer\u2019s Disease by Preserving Mitochondrial Function in APP\/PS1 Mice and 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