JLE

Epileptic Disorders

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Progressive myoclonus epilepsy associated with neuroserpin inclusion bodies (neuroserpinosis) Volume 18, supplement 2, September 2016

Figure 1

Molecular models of serpin conformers. M represents the active protease inhibitor with the reactive loop shown in red and β-sheet A in blue. Mutations that destabilize sheet A (typically in the so-called ‘shutter region’ signified by the red dashed box) allow the partial insertion of the reactive loop to form a new strand in sheet A (M*). The consequent opening of the sheet allows the reactive loop from another serpin to insert forming a serpin dimer (P). The repeated addition of serpins by loop-sheet polymerisation in this way results in large aggregates.

Figure 2

The NMDA receptor mediates the influx of calcium into neurones in the presence of glutamate. tPA has been shown to cleave the NR1 subunit (triangle) of the receptor and, as a consequence, increases the concentration of intracellular calcium. By inhibiting tPA, neuroserpin is thought to protect neurons from the toxic consequences of excessive NMDA activity, termed ‘excitotoxicity’.