Plant sterols: Friend or foe in CNS disorders?

Abstract

In mammals, the central nervous system (CNS) is the most cholesterol rich organ by weight. Cholesterol metabolism is tightly regulated in the CNS and all cholesterol available is synthesized in situ. Deficits in cholesterol homeostasis at the level of synthesis, transport, or catabolism result in severe disorders featured by neurological disability. Recent studies indicate that a disturbed cholesterol metabolism is involved in CNS disorders, such as Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In contrast to circulating cholesterol, dietary plant sterols, can cross the blood-brain barrier and accumulate in the membranes of CNS cells. Plant sterols are well-known for their ability to lower circulating cholesterol levels. The finding that they gain access to the CNS has fueled research focusing on the physiological roles of plant sterols in the healthy and diseased CNS. To date, both beneficial and detrimental effects of plant sterols on CNS disorders are defined. In this review, we discuss recent findings regarding the impact of plant sterols on homeostatic and pathogenic processes in the CNS, and elaborate on the therapeutic potential of plant sterols in CNS disorders.

Plant Glycosides and Glycosidases: A Treasure-Trove for Therapeutics

“…Their chemical structure consists of a sterol body; a cyclopentanoperhydro-phenanthrene ring system (formed by four rigid rings) with a hydroxyl group at position C-3 and a side chain attached to the carbon C-17 ( Figure 2C). Differences in the nature of the side chain gives a plethora of diverse sterols in plants, accounting to more than 260 different ones, as described over the last decades (Vanmierlo et al, 2015). The most abundant phytosterols in human diet are β-sitosterol, campesterol, campestanol, and stigmasterol.…”

Increased flux of the plant sterols campesterol and sitosterol across a disrupted blood brain barrier

“…Based on the finding that the majority of plant sterols are carried in the HDL fraction, it was suggested that SR-B1 may play an important role. These HDL receptors are expressed by the apical endothelial cells of the BBB and could be involved in phytosterol transfer from blood into brain parenchyma (Vanmierlo et al, 2015).…”

“…The mechanism by which glycosylated sitosterol possesses these harmful effects is not clear. It is speculated that it may occur through LXRβ disabling or through hindering mitochondrial function (Vanmierlo et al, 2015).…”

Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging

“…In the complex process of cholesterol biosynthesis the first steroid intermediate lanosterol can be converted to cholesterol through two alternative pathways: the Bloch pathway via desmosterol, a direct cholesterol precursor, and the Kandutsch-Russell pathway via lathosterol. The disturbance in cholesterol homeostasis underlies many neurodegenerative diseases, and with aging represents a major risk factor for the development of such pathologies (Valenza et al 2007;Popp et al 2013;Vanmierlo et al 2015). Data regarding brain cholesterol metabolism in the course of aging are somewhat inconsistent (reviewed in Martin et al 2010).…”