ABSTRACT
Alzheimer's disease (AD), the major cause of dementia, affects the elderly population worldwide. Previous studies have shown that depletion of receptor-interacting protein kinase 1 (RIPK1) expression reverted the AD phenotype in murine AD models. Necroptosis, executed by mixed lineage kinase domain-like (MLKL) protein and activated by RIPK1 and RIPK3, has been shown to be involved in AD. However, the role of RIPK1 in beta-amyloid (Aß)-induced necroptosis is not yet fully understood. In this study, we explored the role of RIPK1 in the SH-SY5Y human neuroblastoma cells treated with Aß 1-40 or Aß 1-42. We showed that Aß-induced neuronal cell death was independent of apoptosis and autophagy pathways. Further analyses depicted that activation of RIPK1/MLKL-dependant necroptosis pathway was observed in vitro. We demonstrated that inhibition of RIPK1 expression rescued the cells from Aß-induced neuronal cell death and ectopic expression of RIPK1 was found to enhance the stability of the endogenous APP. In summary, our findings demonstrated that Aß can potentially drive necroptosis in an RIPK1-MLKL-dependent manner, proposing that RIPK1 plays an important role in the pathogenesis of AD.
Subject(s)
Alzheimer Disease , Neurotoxicity Syndromes , Aged , Alzheimer Disease/genetics , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/toxicity , Animals , Apoptosis , Cell Death , Humans , Mice , Necroptosis , Protein Kinases/genetics , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Receptor-Interacting Protein Serine-Threonine Kinases/metabolismABSTRACT
Diabetes, characterized by hyperglycemia, is one of the most significant metabolic diseases, reaching alarming pandemic proportions. It can be due to the defects in insulin action, or secretion, or both. The global prevalence of diabetes is estimated at 425 million people in 2017, and expected to rise to 629 million by 2045 due to an increasing trend of unhealthy lifestyles, physical inactivity, and obesity. Several treatment options are available to diabetics, however, some of the antidiabetic drugs result in adverse side effects such as hypoglycemia. Hence, there has been a proliferation of studies on natural products with antidiabetic effects, including plants from the Myrtaceae family, such as Psidium guajava, Eucalyptus globulus,Campomanesia xanthocarpa, and more significantly, Syzygium sp. Previous studies have shown that a number of Syzygium species had potent antidiabetic effects and were safe for consumption. This review aims to discuss the antidiabetic potential of Syzygium sp., based on in vitro and in vivo evidence.
