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However, such therapeutic strategies have limited clinical outcomes due to the chronic and irreversible impairment of the nervous system in the late stage of AD. Recently, inflammatory responses, manifested in oxidative stress and glial cell activation, have been reported as hallmarks in the early stages of AD. Based on the crosstalk between inflammatory response and brain cells, a reactive oxygen species (ROS)\u2010responsive dendrimer\u2013peptide conjugate (APBP) is devised to target the AD microenvironment and inhibit inflammatory responses at an early stage. With the modification of the targeting peptide, this nanoconjugate can efficiently deliver peptides to the infected regions and restore the antioxidant ability of neurons by activating the nuclear factor (erythroid\u2010derived 2)\u2010like 2 signaling pathway. Moreover, this multi\u2010target strategy exhibits a synergistic function of ROS scavenging, promoting A\u03b2 phagocytosis, and normalizing the glial cell phenotype. As a result, the nanoconjugate can reduce ROS level, decrease A\u03b2 burden, alleviate glial cell activation, and eventually enhance cognitive functions in APPswe\/PSEN1dE9 model mice. These results indicate that APBP can be a promising candidate for the multi\u2010target treatment of AD.<\/jats:p>","DOI":"10.1002\/adma.202100746","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T07:57:17Z","timestamp":1621238237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":120,"title":["Biomimetic Dendrimer\u2013Peptide Conjugates for Early Multi\u2010Target Therapy of Alzheimer's Disease by Inflammatory Microenvironment Modulation"],"prefix":"10.1002","volume":"33","author":[{"given":"Peixin","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Smart Drug Delivery Ministry of Education State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Department of Pharmaceutics School of Pharmacy Fudan University  Shanghai 201203 P. R. 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