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Protein Aggregation in Health and Neurodegenerative Diseases
Understanding the rules and distinguishing the differences between normal and aberrant protein aggregation is key to answering elemental questions from why we age? to what triggers the early onset of neurodegenerative diseases? We focus on decoding the aggregation pathways of proteins implicated in the pathology of Alzheimer's disease using liquid-based scanning probe microscopy, chemical spectroscopy and machine learning-based data analysis for protein classification in body fluids. To this end, we investigate both protein aggregates at buffered aqueous solution-solid interfaces and in body fluids (blood and cerebrospinal fluid) from individuals at various stages of decline in memory and cognition through a collaborative project with Kantonal Hospital St. Gallen. We aim to establish that clinically relevant information can be obtained and validated at the nanoscopic scale.
(a). The continuum of Alzheimers disease (AD). The onset of AD is nearly 20 years before symptoms such as confusion in time and place becomes visible (b) Summary of research results in profiling protein aggregates on red blood cells confirmed that the size, shape, morphology and prevalence of protein aggregates on RBCs varied depending on age and level of cognitive decline in individuals.
1. Spatial organisation of protein aggregates on RBCs as physical biomarkers of Alzheimer's disease pathology.
Science Advances, 7, 39, eabj2137, 2021.
Peter N. Nirmalraj, Thomas Schneider and Ansgar Felbecker.
2. Complete aggregation pathway of amyloid-β (1-40) and (1-42) resolved on an atomically clean interface.
Science Advances. 6, 15, eaaz6014, 2020.
Peter N. Nirmalraj, Jonathan List, Shayon Battacharya, Geoffrey Howe, Liang Xu, Damien Thompson and Michael Mayer.
3. Single-Particle Resolution of Copper-Associated Annular α-Synuclein Oligomers Reveals Potential Therapeutic Targets of Neurodegeneration. ACS Chemical Neuroscience, 2022 (https://doi.org/10.1021/acschemneuro.2c00021).
Olena. Synhaivska, Shayon. Bhattacharya, Silvia. Campioni, Damien. Thompson and Peter N. Nirmalraj.
Transport at Nanoscale Interfaces Laboratory