Novel mechanisms and approaches in the study of neurodegeneration and neuroprotection. A review

Abstract

Cellular mechanisms involved in neurodegeneration and neuroprotection are continuing to be explored, and this paper focuses on some novel discoveries that give further insight into these processes. Oligodendrocytes and activated astroglia are likely generators of the pro-inflammatory cytokines, such as the tumor necrosis factor family and interleukin family, and these glial support cells express adhesion receptors (e.g., VCAM) and release intercellular adhesion molecules (ICAM) that have a major role in neuronal apoptosis. Even brief exposure to some substances, in ontogeny and sometimes in adulthood, can have lasting effects on behaviors because of their prominent toxicity (e.g., NMDA receptor antagonists) or because they sensitize receptors (e.g., dopamine D2 agonists), possibly permanently, and thereby alter behavior for the lifespan. Cell cycle genes which may be derived from microglia, are the most-recent entry into the neuroprotection schema. Neuroprotection afforded by some common substances (e.g., melatonin) and uncommon substances [e.g., nicotine, green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG), trolox], ordinarily thought to be simple radical scavengers, now are thought to invoke previously unsuspected cellular mechanisms in the process of neuroprotection. Although Alzheimer's disease (AD) has features of a continuous spectrum of neural and functional decline, in vivo PET imaging and and functional magnetic resonance imaging, indicate that AD can be staged into an early phase treatable by inhibitors of beta and gamma secretase; and a late phase which may be more amenable to treatment by drugs that prevent or reverse tau phosphorylation. Neural transplantation, thought to be the last hope for neurally injured patients (e.g., Parkinsonians), may be displaced by non-neural tissue transplants (e.g., human umbilical cord blood; Sertoli cells) which seem to provide similar neurotrophic support and improved behavior - without posing the major ethical dilemma of removing tissue from aborted fetuses. The objective of this paper is to invite added research into the newly discovered (or postulated) novel mechanisms; and to stimulate discovery of additional mechanisms attending neurodegeneration and neuroprotection.

Pomegranate Polyphenols and Resveratrol Protect the Neonatal Brain against Hypoxic-Ischemic Injury

“…Polyphenols have been found to possess antioxidant properties as well as to have effects on gene expression [Kostrzewa and Segura-Aguilar, 2003]. Specifically, one polyphenol, resveratrol, has been shown to increase activity of members of the sirtuin gene class, blunting p53 action and blocking apoptosis [Latruffe et al, 2002;Hall, 2003;Howitz et al, 2003].…”

Maternal Dietary Supplementation with Pomegranate Juice Is Neuroprotective in an Animal Model of Neonatal Hypoxic-Ischemic Brain Injury

“…These compounds have been found to possess antioxidant properties as well as to have effects on gene expression (21). Specifically, one polyphenol, resveratrol, a recognized constituent of red and white grapes and a variety of plants and trees, has been shown to increase activity of members of the sirtuin gene class, blunting p53 action and blocking apoptosis (22)(23)(24).…”

Theaflavin digallate inactivates plasminogen activator inhibitor: Could tea help in Alzheimer's disease and obesity?

“…Green tea polyphenol EGCG and black tea polyphenols are traditionally perceived as simple radical scavengers, although a growing body of evidence reveals their previously unsuspected biochemical activity (4,34,35). The PAI-1 inhibitory activity of theaflavin digallate falls into this category.…”