2020/08/21 by Georg Meisl, Alexander J. Dear, Meisl, Georg +5
Biochemistry, Genetics and Molecular Biology · Medicine · #Alzheimer's disease research and treatments #Biological Physics (physics.bio-ph) #FOS: Biological sciences #FOS: Physical sciences #Metabolomics and Mass Spectrometry Studies #Molecular Networks (q-bio.MN) #Prion Diseases and Protein Misfolding #Protein Structure and Dynamics
paper · pdf · doi:10.48550/arxiv.2008.09699
openalex publication_date 2020/08/21 · openalex created_date 2022/07/26 · openalex updated_date 2026/07/28
The formation and proliferation of protein aggregates play a central role in\na number of devastating neuro-degenerative diseases. Many experimental studies\nindicate that the ability of existing aggregates to replicate is a key property\nin generating their pathogenic effect across a range of diseases. However,\ngiven the complexity of the process in vivo, no principled general approach\ncurrently exists to obtain the rates of the fundamental steps that underlie\naggregate formation from measurements in living systems. In order to address\nthis challenge, here we present a general approach for analysing aggregation\nkinetics that considers broad classes of processes that can be described by a\nfamily of scaling solutions. Our approach is not limited only to fibrillar\naggregates, but applies to any aggregate shape. We show that the rates can\nreliably be extracted by fitting of a simple logistic function, even from\nexperimental data in living systems, and give a very general analytical\nexpression that relates the scaling of the exponential rate with monomer\nconcentration to the microscopic details of the underlying reaction. This\napproach can thus be used to infer the microscopic mechanism driving the\naggregation process from macroscopic measurements in complex systems.\n