Abstracts 2018

ABSTRACT: ROLE OF PRO-INFLAMMATORY S100 PROTEINS IN NEURODEGENERATIVE AMYLOID DISEASE

We would like to present you the abstract of our another keynote speaker – Ludmilla Morozova-Roche – the professor in Medical Biophysics, Department of Medical Biochemistry and Biophysics at the Umeå University, Sweden.

Pro-inflammatory S100A8/A9 proteins are increasingly recognized as important contributors to inflammation-related neurodegeneration. These are small Ca2+ binding EF-hand proteins involved in diverse cellular processes such as cell survival, proliferation, differentiation and danger signaling. The expression level of S100 proteins and among them S100A8 and S100A9 is significantly increased in many types of cancer, inflammatory, neurodegenerative and autoimmune diseases and they are implicated in the numerous disease pathologies. We have demonstrated that S100 proteins are intrinsically amyloidogenic and S100A6, S100A8 and S100A9 are able to form amyloids both in vitro and in vivo in cell models and in neurodegenerative diseases. The specific mechanisms of S100A9 action in Alzheimer’s disease and traumatic brain injuries are discussed, where it contributes to amyloid plaques formation and neural cytotoxicity together with Aβ, potentially playing a leading role in these processes. Recently we have demonstrated that S100A9 can serve as a robust biomarker differentiating early stages of cognitive impairment in Alzheimer’s disease, especially in conjunction with others such as Aβ(1−42) and tau-proteins, which further signifies its involvement in Alzheimer’s disease pathology. The area of interests include also the in vitro studies of the mechanisms and pathways of S100 self-assembly, including kinetic and structural studies, the features of amyloid precursor state and regulatory factors of the amyloid self-assembly process.