Familial encephalopathy with neuroserpin inclusion bodies

Cell biology of the serpinopathies

Cell biology of the serpinopathies

We study a group of protein conformational diseases caused by polymerisation of mutant serpins (serin proteinase inhibitors), specifically the neuronal protein neuroserpin and the hepatic serpin alpha-1 antitrypsin. The mechanism of inhibition of serpins requires a high molecular flexibility that renders them very sensitive to destabilising mutations.

Neuroserpin polymers cause oxidative stress in a neuronal model of the dementia FENIB

The serpinopathies are human pathologies caused by mutations that promote polymerisation and intracellular deposition of proteins of the serpin superfamily, leading to a poorly understood cell toxicity. The dementia FENIB is caused by polymerisation of the neuronal serpin neuroserpin (NS) within the endoplasmic reticulum (ER) of neurons.

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