From a cage to a model, from the heart to the brain : novel concepts in neuroprotection / Sarel Francois Malan

Abstract

Disorders like Parkinson's and Alzheimer's disease Neurodegenerative diseases, such as Parkinson's (PO) and Alzheimer's diseases, are increasingly becoming a burden to society as the world's population is growing older. Neurodegeneration and the development of neuroprotective agents have thus in recent years become an increasingly important focus of research. Currently, relatively good symptomatic therapy for PO exists, but no proven therapy that prevents cell death (neuroprotection), or restores damaged neurons to a normal state (neurorescue) are available. Intracellular calcium homeostasis, or rather the lack thereof, have in many studies been implicated in neuronal degeneration and is currently believed to be one of its main causes. An intracellular calcium overload leads to the activation of various enzyme systems, as well as accumulation of free radicals intracellular. These and other calcium related processes ultimately lead to cell death and neurodegeneration. Previous studies evaluating the biological activity of the polycyclic cage amines indicate activity that includes amongst others, neuroprotective activity and selectivity and high affinity for the sigma-binding site. The pentacycloundecylamine derivatives show structural similarities to known NMOA antagonists and its peripheral L-type calcium channel antagonism as observed in cardiac myositis is well described. Although little is known about the mechanisms of CNS activity of the compounds, it is postulated that these derivatives could yet be of therapeutic value in the treatment of neurodegenerative.