Chemical and Pharmacological Mechanisms of Plant-Derived Neurotoxins

Abstract

The nervous system (NS) comprises the central and peripheral divisions. While the central nervous system (CNS) consists mainly of the brain and spinal cord, the peripheral nervous system (PNS) is subdivided into the somatic nervous system and autonomic nervous system (ANS). The ANS is further subdivided into the sympathetic and parasympathetic systems. In every component of the NS, information passes from one cell to another or from the NS to the muscular system by means of neurotransmitter molecules that are secreted by neurons. All neurotransmitters have a general mode of action, involving binding to a receptor and altering the target cell’s response to a particular signal (the stimulus). The molecular interaction between a neurotransmitter and its receptor induces a conformational change, which, in turn, changes the electrochemical properties of the nerve cell, promoting entry and/or exit of some electrolytes and generation of an action potential, which enables communication between cells. A number of neurotransmitters are known and well understood in terms of their molecular and biological activities [1]. It is also known that exogenous molecules can enter the body, traverse all the way to the NS, and bind to either receptors or their counter-ligands. The binding of exogenous molecules by either means could promote undesirable effects, some of which exert toxic metabolic responses. In a unique mechanism, nerve agents bind to the enzyme acetylcholinesterase (AChE) and inhibit its ability to recycle the neurotransmitter acetylcholine (ACh) across nerve junctions. There are two types of ACh receptor (AChR), namely nicotinic (N) and muscarinic (M) receptors. Among other organisms, plants are known to be sources of an enormous number of neurotoxic molecules [1]. We highlight the most potent neurotoxins related to well-established modes of neurotransmission.