en Tissue Engineering and Cell Biology Tissue Engineering and Cell Biology مقاله کامل Full Length/Original Article <strong>Background: </strong>Alzheimer&rsquo;s disease is one of the neurodegenerative disorders typified by the aggregate of amyloid-&beta; (A&beta;) and phosphorylated tau protein. Oxidative stress and neuroinflammation, because of A&beta; peptides, are strongly involved in the pathophysiology of Alzheimer&rsquo;s disease (AD). Linagliptin shows neuroprotective properties against AD pathological processes through alleviation of neural inflammation and AMPK activation. <strong>Methods: </strong>We assessed the benefits of linagliptin pretreatment (at 10, 20, and 50 nM concentrations), against A&beta;1-42 toxicity (20 &mu;M) in SH-SY5Y cells. The concentrations of secreted cytokines, such as TNF-&alpha;, IL-6, and IL-1&beta;, and signaling proteins, including pCREB, Wnt1, and PKC&epsilon;, were quantified by ELISA. <strong>Results: </strong>We observed that A&beta; led to cellular inflammation, which was assessed by measuring inflammatory cytokines (TNF-&alpha;, IL-1&beta;, and IL-6). Moreover, A&beta;1-42 treatment impaired pCREB, PKC&epsilon;, and Wnt1 signaling in human SH-SY5Y neuroblastoma cells. Addition of Linagliptin significantly reduced IL-6 levels in the lysates of cells, treated with A&beta;1-42. Furthermore, linagliptin prevented the downregulation of Wnt1 in A&beta;1-42-treated cells exposed. <strong>Conclusion: </strong>The current findings reveal that linagliptin alleviates A&beta;1-42-induced inflammation in SH-SY5Y cells, probably through the suppression of IL-6 release, and some of its benefits are mediated through the activation of the Wnt1 signaling pathway. Alzheimer disease, Interleukin-6, Linagliptin, Wnt1 protein 343 348 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-4087-1&slc_lang=en&sid=1 Mohsen Sedighi sedighi1984@yahoo.com 0000-0003-0608-7840 Yes Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran Tourandokht Baluchnejadmojarad moornani@gmail.com 0000-0002-2703-728X No Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mehrdad Roghani bahman19832003@yahoo.com 0000-0002-9209-8484 No Neurophysiology Research Center, Shahed University, Tehran, Iran