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Property "Has-20abstract" (as page type) with input value "Amyloid-20precursor-20protein-20(APP)-20and-20its-20extracellular-20domain,-20soluble-20APP-20alpha-20(sAPPα)-20play-20important-20physiological-20and-20neuroprotective-20roles.-20However,-20rare-20forms-20of-20familial-20Alzheimer's-20disease-20are-20associated-20with-20mutations-20in-20APP-20that-20increase-20toxic-20amyloidogenic-20cleavage-20of-20APP-20and-20produce-20amyloid-20beta-20(Aβ)-20at-20the-20expense-20of-20sAPPα-20and-20other-20non-2Damyloidogenic-20fragments.-20Although-20mitochondrial-20dysfunction-20has-20become-20an-20established-20hallmark-20of-20neurotoxicity,-20the-20link-20between-20Aβ-20and-20mitochondrial-20function-20is-20unclear.-20In-20this-20study-20we-20investigated-20the-20effects-20of-20increased-20levels-20of-20neuronal-20APP-20or-20Aβ-20on-20mitochondrial-20metabolism-20and-20gene-20expression,-20in-20human-20SH-2DSY5Y-20neuroblastoma-20cells.-20Increased-20non-2Damyloidogenic-20processing-20of-20APP,-20but-20not-20Aβ,-20profoundly-20decreased-20respiration-20and-20enhanced-20glycolysis,-20while-20mitochondrial-20DNA-20(mtDNA)-20transcripts-20were-20decreased,-20without-20detrimental-20effects-20to-20cell-20growth.-20These-20effects-20cannot-20be-20ascribed-20to-20Aβ-20toxicity,-20since-20higher-20levels-20of-20endogenous-20Aβ-20in-20our-20models-20do-20not-20cause-20oxidative-20phosphorylation-20(OXPHOS)-20perturbations.-20Similarly,-20chemical-20inhibition-20of-20β-2Dsecretase-20decreased-20mitochondrial-20respiration,-20suggesting-20that-20non-2Damyloidogenic-20processing-20of-20APP-20may-20be-20responsible-20for-20mitochondrial-20changes.-20Our-20results-20have-20two-20important-20implications,-20the-20need-20for-20caution-20in-20the-20interpretation-20of-20mitochondrial-20perturbations-20in-20models-20where-20APP-20is-20overexpressed,-20and-20a-20potential-20role-20of-20sAPPα-20or-20other-20non-2Damyloid-20APP-20fragments-20as-20acute-20modulators-20of-20mitochondrial-20metabolism." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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