ANTIBODIES AND RECEPTORS: From Neuromuscular Junction to Central Nervous System

• Published in: Neuroscience 2020-07, Vol.439, p.48-61
• Main Author: Vincent, Angela
• Format: Article
• Language: English
• Subjects: acetylcholine receptor; antibody; Central Nervous System; Humans; Isaacs Syndrome; Lambert-Eaton Myasthenic Syndrome; muscle specific kinase; Myasthenia Gravis; neurological disease; Neuromuscular Junction; neuromuscular transmission
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2020.03.009

•Review of Ricardo Miledi’s contributions to the first work in the UK on myasthenia gravis.•Subsequent developments in understanding the immunological and physiological basis of different forms of myasthenia.•Expanding recognition of antibody-mediated diseases of both the peripheral and central nervous systems. Myasthenia gravis (MG) is a relatively rare neurological disease that is usually associated with antibodies to the acetylcholine receptor (AChR). These antibodies (Abs) cause loss of the AChRs from the neuromuscular junction (NMJ), resulting in muscle weakness that can be life-threatening. Another form of the disease is caused by antibodies to muscle specific kinase (MuSK) that result in impaired AChR clustering and numbers at the NMJ, and may also interfere with presynaptic adaptive mechanisms. Other autoimmune disorders, Lambert Eaton myasthenic syndrome and acquired neuromyotonia, are associated with antibodies to presynaptic voltage-gated calcium and potassium channels respectively. All four conditions can be diagnosed by specific clinical features, electromyography and serum antibody tests, and can be treated effectively by a combination of pharmacological approaches and procedures that reduce the levels of the IgG antibodies. They form the first of a spectrum of diseases in which serum autoantibodies bind to extracellular domains of neuronal proteins throughout the nervous system and lead to constellations of clinical features including paralysis, sensory disturbance and pain, memory loss, seizures, psychiatric disturbance and movement disorders. This review will briefly summarize the ways in which this field has developed, since the 1970s when considerable contributions were made in Ricardo Miledi’s laboratory at UCL.