SERPINI1 Human, His

Serpin Peptidase Inhibitor, Clade I Member 1, also known as Neuroserpin, is a member of the serpin superfamily of serine proteinase inhibitors. This protein is encoded by the SERPINI1 gene and is primarily secreted by axons in the brain . The recombinant form of this protein, tagged with a His (histidine) tag, is often used in research to facilitate purification and detection.

Neuroserpin is a serine protease inhibitor that specifically inhibits tissue-type plasminogen activator (tPA) and plasmin, but not thrombin . This selective inhibition is crucial for its role in the nervous system, where it is involved in the regulation of axonal growth and synaptic plasticity .

Neuroserpin is predominantly expressed in the central and peripheral nervous systems. It is secreted from the axons of cultured neurons, indicating its significant role in neuronal function . The expression of Neuroserpin is tightly regulated during development and in response to neuronal activity.

The primary function of Neuroserpin is to regulate the activity of tPA, which is involved in the breakdown of blood clots. By inhibiting tPA, Neuroserpin helps to protect neurons from damage and supports the formation and reorganization of synaptic connections . This function is essential for maintaining synaptic plasticity in the adult nervous system.

Neuroserpin acts by forming a stable complex with tPA, thereby preventing it from converting plasminogen to plasmin. This inhibition is crucial for controlling extracellular proteolysis and maintaining the integrity of the extracellular matrix in the nervous system .

The activity of Neuroserpin is regulated at multiple levels, including gene expression, post-translational modifications, and interactions with other proteins. Mutations in the SERPINI1 gene can lead to the accumulation of mutant Neuroserpin polymers, resulting in a condition known as familial encephalopathy with Neuroserpin inclusion bodies (FENIB) . This condition is characterized by the progressive accumulation of Neuroserpin aggregates in the brain, leading to neurodegeneration and epilepsy.

The recombinant form of Neuroserpin, tagged with a His tag, is widely used in research to study its structure, function, and interactions with other proteins. The His tag allows for easy purification and detection of the protein, facilitating various biochemical and biophysical analyses.