Venue : Centre Broca Nouvelle-Aquitaine
Title
Deamidation of human serum albumin and its possible role in Alzheimer’s disease etiology
Abstract
Human serum albumin (HSA) is the most abundant protein in blood accounting for more than half of the protein content. HSA performs several important functions, such as transporting molecules from blood-brain-barrier to kidneys and liver for clearance. We found that asparagine deamidation leading to isoasparate formation causes structural changes in HSA and triggers its aggregation, with greatly diminished carrying capacity for both monomers and aggregates. A link is found between the level of deamidated HSA and the development of Alzheimer’s disease (AD), providing a new promising venue for AD research after the failure of anti-Aß drugs to slow down AD development.
Selected publications
Végvári, A.; Rodriguez, J. E.; Zubarev. R. A. Single Cell Chemical Proteomics (SCCP) Interrogates the Timing and Heterogeneity of Cancer Cell Commitment to Death, BiorXiv, 2021, https://doi.org/10.1101/2021.04.21.440805
Sabatier, P.; Beusch, C. M.; Saei, A. A.; Aoun, M.; Moruzzi, N.; Leijten, N.; Nordenskjöld, M.; Micke, P.; Maltseva, D.; Tonevitsky, A. G.; Millischer, V.; Villaescusa, J. C.; Kadekar, S.; Berggren, P.-O.; Simonson, O.; Grinnemo, K.-H.; Holmdahl, R.; Rodin, S.; Zubarev, R. A. Plurifaceted proteomics method identifies key regulators of translation during stem cells maintenance and differentiation, Nature Commun., under second revision.
Millan-Arino, L.; Yuan, Z.-F.; Oomen, M. E.; Brandenburg, S.; Chernobrovkin, A.; Salignon, J.; Korner, L.; Zubarev, R. A.; Garcia, B. A.; Riedel, C. G. Purification Combined with High-Resolution Mass Spectrometry to Examine Histone Post-Translational Modifications and Histone Variants in Caenorhabditis elegans. Curr. Protoc. Prot. Sci. 2020, 102, e114.
Zhang, X.; Wang, J.; Zubarev, R. A. Slight deuterium enrichment in water acts as an antioxidant: is deuterium a cell growth regulator? Mol & Cell Proteomics, 2020, DOI:10.1074/mcp.RA120.002231
Yang, H.; Lyutvinskiy, Y.; Herukka, S.-K.; Soininen, H.; Rutishauser, D.; Zubarev, R. A. Prognostic polypeptide blood plasma biomarkers of Alzheimer’s disease progression, J Alzheimer’s Disease, 2014, 40, 659-66.
Yang, H.; Wittnam, J. L.; Zubarev, R. A.;* Bayer, T. A. Shotgun brain proteomics reveals early molecular signature in presymptomatic mouse model of Alzheimer’s disease, J Alzheimer’s Disease, 2013, 37, 297-308.
Antila, K.; Lotjonen, J.; Thurfjell, L.; Laine, J.; Massimini, M.; Rueckert, D.; Zubarev, R. A.; Oresic, M.; van Gils, M.; Mattila, J.; Simonsen, A. H.; Waldemar, G.; Soininen, H. The PredictAD project: development of novel biomarkers and analysis software for early diagnosis of the Alzheimer’s disease, Interface Focus, 2013, 3 Article Number: 20120072 DOI: 10.1098/rsfs.2012.0072.
Yang, H.; Lyutvinskiy, Y.; Soininen, H.; Zubarev, R. A. Alzheimer’s disease and mild cognitive impairment are associated with elevated levels of isoaspartyl residues in blood plasma proteins, J. Alzheimer’s Disease, 2011, 27, 113-118.
Bakalkin, G.; Watanabe, H.; Jezierska, J.; Depoorter, C.; Verschuuren-Bemelmans, C.; Bazov, I.; Artemenko, K. A.; Yakovleva, T.; Dooijes, D.; Van de Warrenburg, B. P. C.; Zubarev, R. A.; Kremer, B.; Knapp, P. E.; Hauser, K. F.; Wijmenga, C.; Nyberg, F.; Sinke, R. J.; Verbeek, D. S. Prodynorphin Mutations Cause the Neurodegenerative Disorder Spinocerebellar Ataxia Type 23, Am. J. Human Genetics, 2010, 87, 593-603.
Séminaire co-organisé par Bordeaux Neurocampus et le Département Sciences biologiques et médicales.