Myasthenia gravis and related disorders: Pathology and molecular pathogenesis

• Published in: Biochimica et biophysica acta 2015-04, Vol.1852 (4), p.651-657
• Main Authors: Ha, James C., Richman, David P.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Autoantibodies - immunology; Autoantibodies - metabolism; Botulism; Botulism - genetics; Botulism - immunology; Botulism - metabolism; Botulism - pathology; Child; Child, Preschool; Congenital myasthenic syndrome; Guillain-Barre Syndrome - genetics; Guillain-Barre Syndrome - immunology; Guillain-Barre Syndrome - metabolism; Guillain-Barre Syndrome - pathology; Humans; Lambert-Eaton Myasthenic Syndrome - genetics; Lambert-Eaton Myasthenic Syndrome - immunology; Lambert-Eaton Myasthenic Syndrome - metabolism; Lambert-Eaton Myasthenic Syndrome - pathology; Lambert–Eaton myasthenic syndrome; LDL-Receptor Related Proteins - genetics; LDL-Receptor Related Proteins - immunology; LDL-Receptor Related Proteins - metabolism; Myasthenia gravis; Myasthenia Gravis - genetics; Myasthenia Gravis - immunology; Myasthenia Gravis - metabolism; Myasthenia Gravis - pathology; Neuromuscular junction; Neuromuscular Junction - genetics; Neuromuscular Junction - immunology; Neuromuscular Junction - metabolism; Neuromuscular Junction - pathology; Organophosphate poisoning; Organophosphate Poisoning - genetics; Organophosphate Poisoning - immunology; Organophosphate Poisoning - metabolism; Organophosphate Poisoning - pathology; Receptors, Cholinergic - genetics; Receptors, Cholinergic - immunology; Receptors, Cholinergic - metabolism
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2014.11.022

Disorders affecting the presynaptic, synaptic, and postsynaptic portions of the neuromuscular junction arise from various mechanisms in children and adults, including acquired autoimmune or toxic processes as well as genetic mutations. Disorders include autoimmune myasthenia gravis associated with acetylcholine receptor, muscle specific kinase or Lrp4 antibodies, Lambert–Eaton myasthenic syndrome, nerve terminal hyperexcitability syndromes, Guillain Barré syndrome, botulism, organophosphate poisoning and a number of congenital myasthenic syndromes. This review focuses on the various molecular and pathophysiological mechanisms of these disorders, characterization of which has been crucial to the development of treatment strategies specific for each pathogenic mechanism. In the future, further understanding of the underlying processes may lead to more effective and targeted therapies of these disorders. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. •Diseases of neuromuscular junction result from immune, toxic, genetic pathologies•Most common: autoimmune anti-acetylcholine receptor myasthenia gravis•Lambert-Eaton myasthenic and Guillain-Barre syndromes target presynaptic sites•Botulinum toxin and organophosphates block synaptic transmission•Mutations in various synaptic proteins cause congenital myasthenic syndromes