ReviewCholesterol overload impairing cerebellar function: The promise of natural products

- Structural and function of cerebellar cortex and importance of cholesterol metabolism.
- Cerebellar toxicity of cholesterol and development of Alzheimer disease.
- Natural products and reduction of cholesterol neurotoxicity.
- Statin drugs importance and side effects.

The cerebellum is the part of the brain most involved in controlling motor and cognitive function. The surface becomes convoluted, forming folia that have a characteristic internal structure of three layers including molecular, Purkinje cell, and granular layer. This complex neural network gives rise to a massive signal-processing capability. Cholesterol is a major constituent, derived by de novo synthesis and the blood-brain barrier. Cholesterol is tightly regulated between neurons and glia-that is, astrocytes, microglia, and oligodendrocytes-and is essential for normal brain development. The axon is wrapped by myelin (cholesterol, phospholipids, and glycosphingolipids) and made up of membranes of oligodendrocytes, separated by periodic gaps in the myelin sheath, called nodes of Ranvier. Hypercholesterolemia is associated with increased oxidative stress and the development of neurotoxicity and Alzheimer's disease. Treatment with natural products has been found to support improved brain function and reduce low-density-lipoprotein cholesterol level. Fish oil is one such product; among the many plant products are: Morus alba leaves, fruit, and bark; pomegranate fruit and peel; Barley β - glucans; date palm; and Allium sativum. The therapeutic potential was discussed in relation with the antilipidemic drugs, statins (HMG-CoA reductase inhibitors).