Abstract
Alzheimer’s disease (AD) is a widespread dynamic neurodegenerative malady. Its etiology is still not clear. One of the foremost pathological features is the extracellular deposits of Amyloid-beta (Aβ) peptides in senile plaques. The interaction of Aβ and the receptor for advanced glycation end products at the blood-brain barrier is also observed in AD, which not only causes the neurovascular anxiety and articulation of proinflammatory cytokines, but also directs reduction of cerebral bloodstream by upgrading the emission of endothelin-1 to induce vasoconstriction. In this process, RAGE is deemed responsible for the influx of Aβ into the brain through BBB. In the current study, we predicted the interaction potential of the natural compounds vincamine, ajmalicine and emetine with the Aβ peptide concerned in the treatment of AD against the standard control, curcumin, to validate the Aβ peptide–compounds results. Protein-protein interaction studies have also been carried out to see their potential to inhibit the binding process of Aβ and RAGE. Moreover, the current study verifies that ligands are more capable inhibitors of a selected target compared to positive control with reference to ΔG values. The inhibition of Aβ and its interaction with RAGE may be valuable in proposing the next round of lead compounds for effective Alzheimer’s disease treatment.
Highlights
Alzheimer’s disease (AD) is a common progressive neurodegenerative disease affecting more than 46 million people worldwide
Concerning structural perspectives, amyloid oligomers are spherical [3], surface-active entities [4] prone to form pore-like assemblies in the plasma membrane of brain cells [5].The circulating Aβ toxins are transported by the receptor for advanced glycation end products (RAGE), a multiligand receptor running transversely through the blood-brain barrier (BBB) into the brain
Aβ was found to associate with Vnc through the amino acids Phe19, Phe20, Ala21, Asp23, Ile32, Gly33, Leu34, Met35 and Val36 (Figure 1C, Table 1); with Ajm through the amino acid residues Phe19, Phe20, Ala21, Gly22, Asp23, Ile32, Gly33,Leu34, Met35,and Val36 (Figure 1A, Table 1); and with Eme through the amino acid residues Ala21, Gl22, Asp23, Gly33, Leu34, Met35 and Val36 (Figure 1B, Table 1); as compared to standard curcumin, which was found to associate through the amino acid residues Ala21, Glu22, Asp23, Val24, Gly25, Leu34, Met35, Val36 and Gly37 (Figure 1D, Table 1)
Summary
Alzheimer’s disease (AD) is a common progressive neurodegenerative disease affecting more than 46 million people worldwide. Figures in the USA for the year 2015 reported AD to affect over 5.3 million people, whereby in 2050, it is expected to grow to nearly 1 million new AD cases per year, with an estimated frequency to range from 11 million to 16 million [1]. Concerning structural perspectives, amyloid oligomers are spherical [3], surface-active entities [4] prone to form pore-like assemblies in the plasma membrane of brain cells [5].The circulating Aβ toxins are transported by the receptor for advanced glycation end products (RAGE), a multiligand receptor running transversely through the blood-brain barrier (BBB) into the brain. A RAGE-Aβ toxin interaction at the BBB directs the induction of oxidative stress, inflammatory responses and decreases the cerebral blood flow
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