Oil Palm Phenolics Inhibit theIn VitroAggregation ofβ-Amyloid Peptide into Oligomeric Complexes

Abstract

Alzheimer's disease is a severe neurodegenerative disease characterized by the aggregation of amyloid-β peptide (Aβ) into toxic oligomers which activate microglia and astrocytes causing acute neuroinflammation. Multiple studies show that the soluble oligomers of Aβ42 are neurotoxic and proinflammatory, whereas the monomers and insoluble fibrils are relatively nontoxic. We show that Aβ42 aggregation is inhibited in vitro by oil palm phenolics (OPP), an aqueous extract from the oil palm tree (Elaeis guineensis). The data shows that OPP inhibits stacking of β-pleated sheets, which is essential for oligomerization. We demonstrate the inhibition of Aβ42 aggregation by (1) mass spectrometry; (2) Congo Red dye binding; (3) 2D-IR spectroscopy; (4) dynamic light scattering; (5) transmission electron microscopy; and (6) transgenic yeast rescue assay. In the yeast rescue assay, OPP significantly reduces the cytotoxicity of aggregating neuropeptides in yeast genetically engineered to overexpress these peptides. The data shows that OPP inhibits (1) the aggregation of Aβ into oligomers; (2) stacking of β-pleated sheets; and (3) fibrillar growth and coalescence. These inhibitory effects prevent the formation of neurotoxic oligomers and hold potential as a means to reduce neuroinflammation and neuronal death and thereby may play some role in the prevention or treatment of Alzheimer's disease.

The adhesion and migration of microglia to β-amyloid (Aβ) is decreased with aging and inhibited by Nogo/NgR pathway

“…To fibrillize, Aβ 1–42 and Aβ 42–1 peptides were resuspended in sterile ddH 2 O followed by incubation for 1 week at 37 °C [ 28 , 29 ]. The Congo Red dye binding assay [ 30 ] was used to valid the fAβ.…”

The Potential Mechanisms of the Neuroprotective Actions of Oil Palm Phenolics: Implications for Neurodegenerative Diseases

“…In another in vitro study by Weinberg et al, OPP had inhibited the aggregation of Aβ into oligomers and significantly reduced the cytotoxicity of aggregating neuropeptides in yeast genetically engineered to overexpress these peptides. This inhibition and cytotoxicity reduction activities may suggest the potential of OPP in reducing neuroinflammation and neuronal death, therefore able to prevent or treat Alzheimer's disease [50]. In the brain, the accumulation of Aβ protein is assumed as an early toxic event in the development of Alzheimer's disease, which is the most common form of dementia linked with plaques and tangles in the brain [51].…”

The Role of KLF4 in Alzheimer’s Disease

“…Under inflammatory conditions, such as Aβ accumulation, the release of pro-inflammatory cytokines may be stimulated in the generation of AD ( Griffin and Barger, 2010 ). Neurotoxicity potency and pro-inflammatory potency of soluble Aβ42 oligomers is relatively higher than insoluble fiber deposit ( Selkoe, 1991 ; Weinberg et al, 2018 ). Silence of KLF 4 is able to restore Aβ42-mediated neuroinflammation, and overexpression of KLF 4 can exacerbate Aβ42-mediated neuroinflammation ( Li L. et al, 2017 ).…”