Characterisation of serpin polymers in vitro and in vivo.
Neuroserpin is a member of the serine protease inhibitor or serpin superfamily of proteins. It is secreted by neurones and plays an important role in the regulation of tissue plasminogen activator at the synapse. Point mutations in the neuroserpin gene cause the autosomal dominant dementia familial...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1797079938357002240 |
|---|---|
| author | Belorgey, D Irving, J Ekeowa, U Freeke, J Roussel, B Miranda, E Pérez, J Robinson, C Marciniak, S Crowther, D Michel, C Lomas, D |
| author_facet | Belorgey, D Irving, J Ekeowa, U Freeke, J Roussel, B Miranda, E Pérez, J Robinson, C Marciniak, S Crowther, D Michel, C Lomas, D |
| author_sort | Belorgey, D |
| collection | OXFORD |
| description | Neuroserpin is a member of the serine protease inhibitor or serpin superfamily of proteins. It is secreted by neurones and plays an important role in the regulation of tissue plasminogen activator at the synapse. Point mutations in the neuroserpin gene cause the autosomal dominant dementia familial encephalopathy with neuroserpin inclusion bodies or FENIB. This is one of a group of disorders caused by mutations in the serpins that are collectively known as the serpinopathies. Others include α(1)-antitrypsin deficiency and deficiency of C1 inhibitor, antithrombin and α(1)-antichymotrypsin. The serpinopathies are characterised by delays in protein folding and the retention of ordered polymers of the mutant serpin within the cell of synthesis. The clinical phenotype results from either a toxic gain of function from the inclusions or a loss of function, as there is insufficient protease inhibitor to regulate important proteolytic cascades. We describe here the methods required to characterise the polymerisation of neuroserpin and draw parallels with the polymerisation of α(1)-antitrypsin. It is important to recognise that the conditions in which experiments are performed will have a major effect on the findings. For example, incubation of monomeric serpins with guanidine or urea will produce polymers that are not found in vivo. The characterisation of the pathological polymers requires heating of the folded protein or alternatively the assessment of ordered polymers from cell and animal models of disease or from the tissues of humans who carry the mutation. |
| first_indexed | 2024-03-07T00:53:01Z |
| format | Journal article |
| id | oxford-uuid:870c0eaf-869a-47bd-80d5-42e1503417e1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:53:01Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:870c0eaf-869a-47bd-80d5-42e1503417e12022-03-26T22:08:09ZCharacterisation of serpin polymers in vitro and in vivo.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:870c0eaf-869a-47bd-80d5-42e1503417e1EnglishSymplectic Elements at Oxford2011Belorgey, DIrving, JEkeowa, UFreeke, JRoussel, BMiranda, EPérez, JRobinson, CMarciniak, SCrowther, DMichel, CLomas, DNeuroserpin is a member of the serine protease inhibitor or serpin superfamily of proteins. It is secreted by neurones and plays an important role in the regulation of tissue plasminogen activator at the synapse. Point mutations in the neuroserpin gene cause the autosomal dominant dementia familial encephalopathy with neuroserpin inclusion bodies or FENIB. This is one of a group of disorders caused by mutations in the serpins that are collectively known as the serpinopathies. Others include α(1)-antitrypsin deficiency and deficiency of C1 inhibitor, antithrombin and α(1)-antichymotrypsin. The serpinopathies are characterised by delays in protein folding and the retention of ordered polymers of the mutant serpin within the cell of synthesis. The clinical phenotype results from either a toxic gain of function from the inclusions or a loss of function, as there is insufficient protease inhibitor to regulate important proteolytic cascades. We describe here the methods required to characterise the polymerisation of neuroserpin and draw parallels with the polymerisation of α(1)-antitrypsin. It is important to recognise that the conditions in which experiments are performed will have a major effect on the findings. For example, incubation of monomeric serpins with guanidine or urea will produce polymers that are not found in vivo. The characterisation of the pathological polymers requires heating of the folded protein or alternatively the assessment of ordered polymers from cell and animal models of disease or from the tissues of humans who carry the mutation. |
| spellingShingle | Belorgey, D Irving, J Ekeowa, U Freeke, J Roussel, B Miranda, E Pérez, J Robinson, C Marciniak, S Crowther, D Michel, C Lomas, D Characterisation of serpin polymers in vitro and in vivo. |
| title | Characterisation of serpin polymers in vitro and in vivo. |
| title_full | Characterisation of serpin polymers in vitro and in vivo. |
| title_fullStr | Characterisation of serpin polymers in vitro and in vivo. |
| title_full_unstemmed | Characterisation of serpin polymers in vitro and in vivo. |
| title_short | Characterisation of serpin polymers in vitro and in vivo. |
| title_sort | characterisation of serpin polymers in vitro and in vivo |
| work_keys_str_mv | AT belorgeyd characterisationofserpinpolymersinvitroandinvivo AT irvingj characterisationofserpinpolymersinvitroandinvivo AT ekeowau characterisationofserpinpolymersinvitroandinvivo AT freekej characterisationofserpinpolymersinvitroandinvivo AT rousselb characterisationofserpinpolymersinvitroandinvivo AT mirandae characterisationofserpinpolymersinvitroandinvivo AT perezj characterisationofserpinpolymersinvitroandinvivo AT robinsonc characterisationofserpinpolymersinvitroandinvivo AT marciniaks characterisationofserpinpolymersinvitroandinvivo AT crowtherd characterisationofserpinpolymersinvitroandinvivo AT michelc characterisationofserpinpolymersinvitroandinvivo AT lomasd characterisationofserpinpolymersinvitroandinvivo |