Peripheral Administration of a Cell-Penetrating MOTS-c Analogue Enhances Memory and Attenuates Aβ_1–42- or LPS-Induced Memory Impairment through Inhibiting Neuroinflammation

MOTS-c is a 16-amino acid mitochondrial derivative peptide reported to be involved in regulating insulin and metabolic homeostasis via the AMP activated protein kinase (AMPK). AMPK agonist AICAR has been improve cognition. Previous reports also pointed out that may effective as therapeutic option toward prevention of aging processes. Therefore, we investigated roles memory recognition process. The results showed central not only enhanced object location formation consolidation but ameliorated deficit induced by Aβ1–42 or LPS. memory-ameliorating effects could blocked inhibitor dorsomorphin. Moreover, treatment significantly increased phosphorylation ERK, JNK, p38 hippocampus. underlying mechanism neuroprotection involve inhibiting activation astrocytes microglia production proinflammatory cytokines. In addition, found peripheral administration does cross blood–brain barrier (BBB) plays an effect. order brain intake MOTS-c, screen (PRR)5, cell penetrating peptides, carrier for into brain. Then NOR task, intranasal intravenous MP (cell-penetrating analogue) good performance on formation, consolidation, impairment. Near-infrared fluorescent experiments real-time biodistribution after infusion MP. These suggested might new potential target cognitive decline AD.