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  • A has been reported to decrease insulin receptors and

    2023-01-16

    Aβ has been reported to decrease insulin receptors and impair insulin signaling in neurons, preventing phosphorylation of Akt and glycogen synthase kinase 3β (GSK-3β), downstream of insulin signaling, and to increase phosphorylation of tau protein causing neurofibrillary tangles (Tokutake et al., 2012, Zhao et al., 2008). Furthermore, it was reported that insulin concentration in cerebrospinal fluid decreased in severe AD patients (Craft et al., 1998) and that Aβ reduced insulin synthesis in cultured neurons (Nemoto et al., 2013). These results suggest that Aβ might decrease insulin levels in molecular weight and impair insulin signaling to cause insulin resistance and AD pathology (Bedse et al., 2015). Insulin expression in brain has been investigated mainly in neurons as described above; however, insulin synthesis in astrocytes and the effects of Aβ on it have not been reported for details. On the other hand, astrocytic activation is well-reported in AD brain, and lipopolysaccharide (LPS) is a well-known experimental activator of glial cells (Huang et al., 2017, Takano et al., 2011). In the present study, we investigated whether astrocytes expressed and produced insulin protein and Aβ affected astrocytic insulin synthesis. We assessed the expression of insulin both of mRNA and protein levels in cultured rat astrocytes, and the effects of Aβ and LPS on astrocytic insulin expressions.
    Materials and methods
    Results
    Discussion
    Conclusion
    Introduction Alzheimer's disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks. Alzheimer's disease is featured by the accumulation of Amyloid-β (Aβ) peptide and neurofibrillary tangles in the regions of hippocampus and cerebral cortex [1], [2], [3]. Aβ peptide is a complex biological molecule, which interacts with many types of receptors and/or forms insoluble assemblies, and eventually, its non-physiological depositions alternate with the normal neuronal conditions. When not properly cleared from the brain, it builds up into plaques that destroy synapses, the junctions between nerve cells, resulting into cognitive decline and memory loss. Currently, the exact pathology of Alzheimer's disease is not well known, but it is widely believed that deposition of Aβ peptide is one main cause leading to the degeneration and death of neurons [4], [5], [6]. Due to the pivotal role of Aβ peptide in the pathobiology of Alzheimer's disease, a great deal of effort has been made to reveal its exact role in neuronal dysfunctions and to finding efficacious therapeutic strategies against its adverse neuronal outcomes. Aβ peptide is formed by proteolytic cleavage of the amyloid precursor protein (APP) and is associated with the formation of amyloid deposits in Alzheimer's disease [7], [8]. The formation of fibrillar amyloid deposits is accompanied by conformational changes of the soluble Aβ peptide in the random coil or α-helical structure into β-sheet structures [8], [9]. Since structural studies of Aβ peptides are often limited due to their high aggregation tendency, solvent conditions need to be carefully chosen. Several strategies have been considered to prevent or reduce Aβ aggregation including a variety of molecules that have been considered as inhibitors of amyloid aggregation [10], [11], [12], [13], [14], [15], [16], [17]. One such molecule is trehalose, a natural disaccharide widely existing in varieties of organisms and daily food [18]. Trehalose has been utilized extensively in the food industry and has been demonstrated to have several unique properties including its potential utility in preventing neurodegeneration. Trehalose is known to have extraordinary properties in terms of its ability to help preserve protein structural integrity in stressful conditions and thereby avoiding their denaturation, and by acting as a chemical chaperone to reduce aggregation of pathologically misfolded proteins [19], [20].