Journal
EPILEPTIC DISORDERS
Volume 18, Issue -, Pages S103-S110Publisher
JOHN LIBBEY EUROTEXT LTD
DOI: 10.1684/epd.2016.0847
Keywords
serpins; serpinopathy; protease inhibitor; conformational disease; neuroserpin; dementia; familial progressive myoclonic epilepsy; FENIB; progressive myoclonus epilepsies
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Funding
- Medical Research Council [MR/N024842/1, G0901786] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10070] Funding Source: researchfish
- MRC [MR/N024842/1, G0901786] Funding Source: UKRI
- Medical Research Council [G0901786, MR/N024842/1] Funding Source: Medline
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Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a conformational proteinopathy characterised by neuronal inclusion bodies composed of the serine protease inhibitor (SERPIN), neuroserpin. Presenting clinically as a familial dementia-epilepsy syndrome, the molecular mechanism of the pathogenic abnormalities in neuroserpin has been characterised at atomic resolution. There is a remarkable genotype-phenotype correlation between the degree of molecular destabilisation of the several variants of the neuroserpin protein, their propensity to self-associate and the age of onset of the dementia-epilepsy complex. As with other serpinopathies there appears to be a mix of cell-autonomous toxicity, due to neuronal accumulation of neuroserpin, and non-cell autonomous toxicity, caused by loss of protease inhibition, in this case the dysregulated protease is likely to be tissue plasminogen activator (tPA). FENIB should be considered in cases of progressive myoclonic epilepsy and dementia particularly where there is family history of neuropsychiatric disease.
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