Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Cátedra de Inmunología, Buenos Aires, Argentina; CONICET, Universidad de Buenos Aires, Instituto de Estudios de la Inmunidad Humoral "Prof. Dr. Ricardo A. Margni" (IDEHU), Buenos Aires, Argentina.
Laboratory of Molecular Neurobiology, Biomedical Research Institute (BIOMED), UCA, CONICET, Av. Alicia Moreau de Justo 1600, C1107AFF, Buenos Aires, Argentina.
Arch Biochem Biophys. 2021 Apr 15;701:108788. doi: 10.1016/j.abb.2021.108788. Epub 2021 Feb 4.
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 among which myasthenia gravis stands out can impact on this rapid and efficient signaling mechanism, including autoimmune diseases affecting the nicotinic receptor or other synaptic proteins. 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.
胆碱能神经肌肉接头是运动神经元末梢和骨骼肌纤维之间的典型外周突触。在脊椎动物中，乙酰胆碱从突触前部位释放出来，与突触后膜上的烟碱型乙酰胆碱受体结合。许多病理情况都会影响这种快速而有效的信号传递机制，其中包括影响烟碱受体或其他突触蛋白的自身免疫性疾病。胆固醇是生物膜的重要组成部分，特别是在突触后膜中含量丰富，它与烟碱型乙酰胆碱受体相互作用并调节其许多特性。重症肌无力对突触后膜造成的深刻变化必然涉及胆固醇。本文分析了重症肌无力病理生理学和相关突触后膜功能障碍的一些方面，包括抗体-受体相互作用引起的肌细胞胆固醇代谢失调。此外，鉴于他汀类药物作为典型的降胆固醇药物的广泛治疗用途，我们还讨论了它们对骨骼肌的影响，以及对慢性使用此类化合物的重症肌无力患者的可能影响。
