Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is one of the utmost chronic neurodegenerative disorders, which is characterized from a neuropathological point of view by the aggregates of amyloid beta (Aβ) peptides that are deposited as senile plaques and tau proteins which form neurofibrillary tangles (NFTs). Even though advancement has been observed in order to understand AD pathogenesis, currently available therapeutic methods can only deliver modest symptomatic relief. Interestingly, naturally occurring dietary flavonoids have gained substantial attention due to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties as alternative candidates for AD therapy. Experimental proof provides support to the idea that some flavonoids might protect AD by interfering with the production and aggregation of Aβ peptides and/or decreasing the aggregation of tau. Flavonoids have the ability to promote clearance of Aβ peptides and inhibit tau phosphorylation by the mTOR/autophagy signaling pathway. Moreover, due to their cholinesterase inhibitory potential, flavonoids can represent promising symptomatic anti-Alzheimer agents. Several processes have been suggested for the aptitude of flavonoids to slow down the advancement or to avert the onset of Alzheimer’s pathogenesis. To enhance cognitive performance and to prevent the onset and progress of AD, the interaction of flavonoids with various signaling pathways is proposed to exert their therapeutic potential. Therefore, this review elaborates on the probable therapeutic approaches of flavonoids aimed at averting or slowing the progression of the AD pathogenesis.

Natural Polyhydroxy Flavonoids, Curcuminoids, and Synthetic Curcumin Analogs as α7 nAChRs Positive Allosteric Modulators

“…Flavonoids have been extensively used in traditional herbal medicine [ 24 ], having important biological effects associated to a wide spectrum of pharmacological activity. They play preventive and therapeutic roles in several pathological processes like arthritis [ 25 ], neurodegenerative [ 26 , 27 , 28 ] and cardiovascular processes [ 29 ], cancer [ 30 ], or pain [ 31 , 32 ]. Several studies revealed that the biological actions of some flavonoids are in part mediated by their ability to modulate the activity of some ion channels, for instance, the cholinergic nicotinic channels.…”

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

“…In healthy people, Aβ production rate (ie, 7.6%) is normally lower than its rate of clearance (ie, 8.3%) per hour. 8 In AD, APP is processed by βfollowed by γ-secretases, resulting in amyloidogenic pathway and causing the formation of Aβ protein fragments of 40 (Aβ 40 ) or of 42 (Aβ 42 ) amino acid length. As this latter can aggregate in insoluble amyloid fibrils, when the ratio between Aβ 42 /Aβ 40 is imbalanced towards Aβ 42 , oligomers formation prevails, extracellular amyloid plaques are deposited and, in turn, synaptic structure and plasticity alterations sustained a cognitive decline.…”

“…Data showed how resveratrol could reach the brain and inhibit the formation and aggregation of Aβ peptides. 8,85 Another very interesting flavonoid is quercetin. Its applications are best studied in targeting cancer.…”

Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer’s Disease

“…Hyperphosphorylation and aggregation of tau is another major hallmarks of AD ( Uddin et al., 2020h : Uddin et al., 2020g ). Accumulating evidence suggested that cannabinoids also play a significant role in tau pathology.…”