LAUSR

The cholinergic neuromuscular junction is the paradigm peripheral synapse between a motor neuron nerve ending and a skeletal muscle fiber. In vertebrates, acetylcholine is released from the presynaptic site and binds to the nicotinic acetylcholine receptor at the postsynaptic membrane. A variety of pathologies can impact on this rapid and efficient signaling mechanism, including autoimmune diseases affecting the nicotinic receptor or other synaptic proteins, among which myasthenia gravis stands out. Cholesterol is an essential component of biomembranes and is particularly rich at the postsynaptic membrane, where it interacts with and modulates many properties of the nicotinic receptor. The profound changes inflicted by myasthenia gravis on the postsynaptic membrane necessarily involve cholesterol. This review analyzes some aspects of myasthenia gravis pathophysiology and associated postsynaptic membrane dysfunction, including dysregulation of cholesterol metabolism in the myocyte brought about by antibody-receptor interactions. In addition, given the extensive therapeutic use of statins as the typical cholesterol-lowering drugs, we discuss their effects on skeletal muscle and the possible implications for MG patients under chronic treatment with this type of compound.