Pleiotropic protective effects of phytochemicals in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD.

Figure 1

Chemical structures of Curcumin. Curcumin belongs to the class of curcuminoids and the presence of double bonds increases its potency and reactivity. The phytochemical curcumin undergoes keto-enol tautomerism.

Figure 2

Reaction mechanism of curcumin with free radicals. The reactions produce phenoxyl radicals and carbon-centered radical at the methylene CH₂ group.

Figure 3

Chemical structure of (−)-Epigallocatechin-3-gallate. EGCG contains three heterocyclic rings, A, B, and C, and the free radical scavenging property of EGCG is attributed to the presence of trihydroxyl group on the B ring and the gallate moiety at the 3′  position in the C ring.

Figure 4

Chemical structure of resveratrol. The 4′-OH in resveratrol provides its chemical and biological features.The transfer of protons or hydrogen atoms to reactive species appears to be crucial to its antioxidant mechanism.