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Biomedical Sciences Research Seminar Series

Transglutaminase 2 in calcium homeostasis and neurodegeneration

Atomic structure of a biological molecule
Seminars

As part of the School of Science and Technology Biomedical Sciences Research Centre Seminar Series, Elisa Tonoli, Nottingham Trent University presents: Transglutaminase 2 in calcium homeostasis and neurodegeneration.

  • From: Wednesday 22 January 2020, 1.10 pm
  • To: Wednesday 22 January 2020, 2 pm
  • Location: ERD 282, Erasmus Darwin, Nottingham Trent University, Clifton Campus, Clifton Lane, Nottingham, NG11 8NS
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Event details

As part of the School of Science and Technology Biomedical Sciences Research Centre Seminar Series, Elisa Tonoli, Nottingham Trent University presents: Transglutaminase 2 in calcium homeostasis and neurodegeneration.

Abstract

Transglutaminase 2 (TG2) is a calcium-dependent protein crosslinking enzyme activated in misfolding diseases and it is implicated in multiple disorders linked to calcium dysregulation, including neurodegeneration. In vitro, TG2 has been involved in the generation of toxic amyloid-β (Aβ) oligomers, and Aβ and tau are substrates of TG2-mediated transamidation in brain. Literature data suggest that TG2 is abnormally activated in the early stages of Alzheimer’s disease (AD), thus blocking its activity may represent a new therapeutic approach. TG2 is also involved in cell-matrix dynamics and has been suggested to be a cargo of extracellular vesicles (EVs) in cancer and tissue fibrosis. EVs have been implicated in the spreading of pathogenic proteins in neurodegeneration and represent a new research field in dementia. In our study we aimed to: i. investigate the role of extracellular TG2 in neuron-glia cross-talk in the context of neurodegeneration; ii. explore substrates of TG2 post-translational modification in a cell model of AD; iii. evaluate TG2 as a potential marker of dementia. Both primary cell models (embryonic rat brain cells) and biological samples from dementia patients were analysed. We found that elevated levels of extracellular TG2 consistently increased basal calcium concentration in hippocampal neurons, affecting calcium homeostasis which is at the basis of neuronal functions. We confirmed previous evidence showing that astrocytes are a rich source of extracellular TG2 in brain and revealed for the first time that TG2 is released in association with astrocytic small EVs. We identified 11 substrates of TG2 transamidation in a cell model mimicking AD using a global quantitative proteomic approach (SWATH™-MS/MS proteomics). Finally, analysis of plasma from dementia patients and healthy controls by an optimised ELISA revealed no significant changes among the cohorts. Our preliminary data suggest that quantitation of TG2 in plasma-derived EVs would enable a more accurate and sensitive evaluation.

Hosted by Dr Elisabetta Verderio-Edwards

All welcome.

For any enquiries please contact Dr Amanda Coutts

Location details

Room/Building:

ERD 282, Erasmus Darwin

Address:

Nottingham Trent University
Clifton Campus
Clifton Lane
Nottingham
NG11 8NS

Past event

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