Neuroprotective effects of resveratrol on damages of mouse cortical neurons induced by β‐amyloid through activation of SIRT1/Akt1 pathway

Abstract

Resveratrol (3,5,4'-tihydroxy-trans-stilbene), a polyphenolic phytoalexin found in the skin and seeds of grapes, has been reported to possess a wide range of biological and pharmacological activities including antioxidant, anti-inflammatory, and antimutagenic effects. The present study intended to explore the neuroprotective effects of resveratrol against Aβ25-35 -induced neurotoxicity of cultured mouse cortical neurons and the possible mechanisms involved. For this purpose, mouse cortical neurons were cultured and exposed to 30 μM Aβ25-35 in the absence or presence of resveratrol (5, 10, and 25 μM). In addition, the potential contribution of the SIRT1/Akt1 neuroprotective pathway in resveratrol-mediated protection against Aβ25-35 -induced neurotoxicity was also investigated. The results showed that resveratrol dose-dependently increased cell viability and reduced the number of apoptotic cells as measured by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) activity assay, reactive oxygen species (ROS) activity assay, and Hoechst/PI double staining. Further study revealed that resveratrol through activation of SIRT1/Akt1 to avert apoptosis. These findings raise the possibility that resveratrol may be a potent therapeutic compound against the neurodegenerative diseases.

Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease

“…The level of activity of SIRT1 can affect the balance of the programmed death pathways of apoptosis and autophagy that ultimately determine cell survival as well as alter the course of stem cell development, maintenance, and differentiation. For example, SIRT1 activity is required for neuronal cell protection (126, 154, 155) and vascular cell survival (23, 78, 79, 156). This necessary fine control of SIRT1 activity also translates into the world of miRNAs such that in several circumstances loss of SIRT1 activity that is controlled by high miRNA expression can be toxic to cell survival and stem cell maintenance.…”

WISP1: Clinical Insights for a Proliferative and Restorative Member of the CCN Family

“…Of the seven mammalian homologues of Sir2 that include SIRT1 through SIRT7, SIRT1 plays a significant role in oxidative stress, cell metabolism, genomic stability, cell survival, neurodegenerative disease, infection, and cardiovascular disease [102–107]. In regards to cytoprotection, SIRT1 activation can prevent hypoxic injury in retinal ganglion cells [108], modulate cell longevity [109, 110], protect against high-fat diet-induced metabolic abnormalities [111, 112], increase cellular survival during anoxia and ischemia [113, 114], reduce Aβ toxicity [115], reverse impaired fat and glucose metabolism [12, 116–118], maintain mitochondrial processing and quality through autophagy [119], foster cellular protection against radiation [120], protect against renal cell aging [121], block apoptotic pathways in preadipocytes [122], and modulate forkhead mediated apoptotic pathways [53, 72, 96, 118, 123–126]. Yet, other studies suggest that to achieve cytoprotection through sirtuin pathways, the level of sirtuin activity may be critical [53, 72, 115, 127], since SIRT1 gene polymorphisms may affect protein expression during cardiovascular disease [105], SIRT1 activity can promote tumor growth [128, 129], and reduction in SIRT1 activity has been reported to enhance the cytoprotective effects of IGF-1 [130].…”

“…Yet, enhanced SIRT1 activity may lead to tumor growth [128, 129]. In addition, some protective mechanisms appear to require a limited activation of SIRT1 [53, 72, 115, 127] and others may necessitate an actual reduction in SIRT1 activity, such as those with IGF-1 [130]. In consideration of mTOR, WISP1 requires activation of mTOR signaling with inhibition of specific pathways such as PRAS40 to offer cellular protection against Aβ exposure [152, 180].…”

Programming Apoptosis and Autophagy with Novel Approaches for Diabetes Mellitus

“…Importantly, the level of SIRT1 activity can yield significant consequences for cellular protection. Insufficient SIRT1 activity can be detrimental for vascular cell survival (105, 193, 256), protection against cardiovascular disease (85), and prevention of neuronal injury (174, 257, 258). However, a reduction in SIRT1 activity also may be required to promote cellular survival in systems involving trophic factors such as as insulin growth factor-1 (259).…”

“…SIRT1 also can increase insulin signaling in insulin-sensitive organs through pathways that involve Akt and PI 3-K (105, 131, 193, 258, 283, 284) as well as stimulate glucose-dependent insulin secretion from pancreatic β cells by repressing UCP2 (285). Regulation of insulin sensitivity by SIRT1 may require AMPK.…”