Abstract
Alzheimer’s disease is a neurodegenerative disorder for which there is a continuous search of drugs able to reduce or stop the cognitive decline. Beta-amyloid peptides are composed of 40 and 42 amino acids and are considered a major cause of neuronal toxicity. They are prone to aggregation, yielding oligomers and fibrils through the inter-molecular binding between the amino acid sequences (17–42) of multiple amyloid-beta molecules. Additionally, amyloid deposition causes cerebral amyloid angiopathy. The present study aims to identify, in the existing literature, natural plant derived products possessing inhibitory properties against aggregation. The studies searched proved the anti-aggregating effects by the thioflavin T assay and through behavioral, biochemical, and histological analysis carried out upon administration of natural chemical compounds to transgenic mouse models of Alzheimer’s disease. According to our present study results, fifteen secondary metabolites from plants were identified which presented both evidence coming from the thioflavin T assay and transgenic mouse models developing Alzheimer’s disease and six additional metabolites were mentioned due to their inhibitory effects against fibrillogenesis. Among them, epigallocatechin-3-gallate, luteolin, myricetin, and silibinin were proven to lower the aggregation to less than 40%.
Highlights
Despite decades of preclinical and clinical research, Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder that involves several pathogenetic mechanisms is still a major and increasing challenge in terms of global health [1,2]
The authors of this review did not find studies using transgenic mouse models developing AD to which one of the latter five plant secondary metabolites were administered as drugs
Considering the fact that through the cleavage of amyloid precursor protein isoform 695 existing mainly in the membranes of the neurons by beta- and gamma-secretases and by the cleavage of the isoform 770 of amyloid precursor protein existing mainly in other tissues of the human body a soluble form of amyloid beta peptide results, the authors propose a mechanism in which the secondary metabolites could bind the soluble form of Aβ in blood and could even cross blood–brain barrier and bind soluble Aβ peptides in the CNS reducing their aggregation
Summary
Despite decades of preclinical and clinical research, Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder that involves several pathogenetic mechanisms is still a major and increasing challenge in terms of global health [1,2]. The cleavage of amyloid precursor proteins (APP) by β- and γ-secretase to the Aβ peptides followed by soluble Aβ monomers aggregate to β-sheet-rich oligomers and insoluble amyloid fibrils yields in the extracellular medium to senile plaques. Proteins (APP) by β- and γ-secretase to the Aβ peptides followed by soluble Aβ monomers aggregate Btoiomβo-lsehcueleest2-r0i2c0h, 10o,l8ig70omers and insoluble amyloid fibrils yields in the extracellular medium to s2eonfi2le plaques. CBoiommpolleecutleelsy20r2e0p, 1li0c,a8t7e0s the most important features of human AD, in vivo models provide context3aonf d21 relevance insight into the pathological alterations that define this condition [32,33,34,35,36]. Liu et al investigated the capacity of gallic acid to block the formation of amyloid-beta fibrils using a solution of 50 μM Aβ(1-40) incubated during 10 h and thioflavin T assay.
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