Unravelling the structure of toxic protein aggregates in situ
Protein aggregation is a hallmark of many neurodegenerative diseases, including Huntington’s, Parkinson’s and amyotrophic lateral sclerosis. However, the mechanisms linking aggregation to neurotoxicity remain poorly understood, partly because only limited information is available on the native structure of protein aggregates inside cells. We address this pressing issue utilizing the latest developments in cryo-electron tomography (cryo-ET). We prepare thin lamellas of vitrified cells containing protein aggregates using cryo-focused ion beam, and subsequently image them in three dimensions by cryo-ET. This allows us to analyse aggregate structure within pristinely preserved cellular environments and at molecular resolution [1, 2]. Here, I will discuss how our latest results shed new light into the cellular mechanisms of neurodegeneration.
Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Goettingen, Goettingen, Germany
Institute of Neuropathology, University Medical Center Goettingen