Molecular Pathology of Neurodegenerative Diseases by Cryo-EM of Amyloids

Overview

Journal Nature

Specialty Science

Date 2023 Sep 27

PMID 37758888

Authors

Sjors H W Scheres

Benjamin Ryskeldi-Falcon

Michel Goedert

Affiliations

Soon will be listed here.

Abstract

Abnormal assembly of tau, α-synuclein, TDP-43 and amyloid-β proteins into amyloid filaments defines most human neurodegenerative diseases. Genetics provides a direct link between filament formation and the causes of disease. Developments in cryo-electron microscopy (cryo-EM) have made it possible to determine the atomic structures of amyloids from postmortem human brains. Here we review the structures of brain-derived amyloid filaments that have been determined so far and discuss their impact on research into neurodegeneration. Whereas a given protein can adopt many different filament structures, specific amyloid folds define distinct diseases. Amyloid structures thus provide a description of neuropathology at the atomic level and a basis for studying disease. Future research should focus on model systems that replicate the structures observed in disease to better understand the molecular mechanisms of disease and develop improved diagnostics and therapies.

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