Role of Resveratrol and its Analogues in the Treatment of Neurodegenerative Diseases: Focus on Recent Discoveries

Abstract

Neurodegenerative diseases are a group of chronic, progressive disorders characterized by the gradual loss of neurons in several areas of the central nervous system (CNS). Substantial evidence has documented a common inflammatory mechanism in neurodegeneration. It is known that classical anti-inflammatory agents, steroids and nonsteroidal anti-inflammatory drugs, have not played a major role in the management of CNS inflammatory conditions. This may be partly due to the natural compartmentation of the brain by the blood-brain barrier. Thus, there is much interest in developing novel anti-inflammatory drugs that may help to prevent or ameliorate CNS inflammation. Resveratrol (RSV) has received considerable attention over the last several decades. Experimental studies have revealed its benefits in several human disease models, including cardio- and neuro-protection, immune regulation and cancer chemoprevention. The broad action spectrum of RSV is explained by the involvement of numerous signaling networks and cellular effector mechanisms. Among them, apoptotic and antioxidant targets have been implicated. Recently, also anti-neuroinflammatory activity has been observed. A number of studies demonstrated that RSV mediates the downregulation of various inflammatory biomarkers such as tumor necrosis factor, cyclooxygenase 2, inducible nitric oxide synthase and interleukins. This activity seems to depend on some structural features of RSV such as the number and the position of hydroxyl groups. In this review, a comprehensive account of multiple intracellular RSV targets involved in neuroinflammation and its analogues design will be treated, pointing to structure/activity relationships.

Amelioration of Aluminum- And Fluoride-Induced Behavioral Alterations Through Resveratrol in Rats.

“…This result is in accordance with the previous studies [26][27][28][29][30], whereas the SLM function was significantly reversed in the resveratrol treated against aluminum along with fluoride-treated group as compared to the aluminum along with fluoride-treated group, showing the protective effect of resveratrol. This observation is in agreement with the earlier findings showing protection of resveratrol against neurodegeneration and preserves cognitive function [31][32][33]. Resveratrol alone treated group did not show any changes as compared to the control group.…”

A genomics approach identifies selective effects of trans-resveratrol in cerebral cortex neuron and glia gene expression

“…In this regard, 22 out of the 26 selected genes whose expression is significantly affected by the use of RSV are down-regulated. Therefore, it seems that the reported beneficial effect of RSV in CNS alterations [see [17] for review] correlates with simultaneous reduction of the expression of different genes. Network analysis showed that among interconnected genes (under moderate stringent parameters) all but Pkp4 were down-regulated.…”

Resveratrol and para-coumarate serve as ring precursors for coenzyme Q biosynthesis

“…Other family members of carotenoid cleavage enzyme in bacteria and fungi cleave resveratrol to produce 4-hydroxy-benzaldehyde and 3,5-dihydroxy-benzaldehyde ( 45,46 ). Notably the 4 ′ hydroxyl group of resveratrol has been identifi ed as crucial for antioxidant and neuroprotective effects of stilbenoids ( 47 ). It seems likely that other stilbenoids may serve as ring precursors of Q.…”