LAUSR

Low-density lipoprotein receptor-related protein 4 (LRP4) is crucial membrane protein in the development and function of neuromuscular junctions and motor neurons. And, it is currently known myasthenia gravis (MG) is caused by antibodies to the acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and LRP4. MuSK and LRP4 are coreceptors for agrin in the signaling pathway that causes clustering of AChR. We demonstrated anti-LRP4 antibodies played a key role in MG. LRP4 is essential for maintaining the structural and functional integrity of the neuromuscular junction and that loss of muscle LRP4 in adulthood alone is sufficient to cause myasthenic symptoms. MG with anti-LRP4 antibodies (LRP4-MG) is considered a rare subtype of MG, however, LRP4 autoantibodies have been recently detected in some motor neuron disease (MND) patients, and LRP4 is required for presynaptic and postsynaptic differentiation. We developed the luciferase immunoprecipitation systems for LRP4 autoantibodies detection and with this assay we studied for four years the sera from Japanese patients who had been suspected of MG or other neurological diseases with general myasthenia and/or muscle weakness. The clinical and therapeutic implications of the anti-LRP4 antibody positivity remain to be clarified, and further studies are necessary to elucidate the pathogenic potential of these autoantibodies.