Prion-like transmission of protein aggregates in neurodegenerative diseases

By P. Brundin, R. Melki, R. Kopito. Nature reviews. Molecular cell biology, 2010

780 citations recorded by the source corpus.

Neurodegenerative diseases are commonly associated with the accumulation of intracellular or extracellular protein aggregates. Recent studies suggest that these aggregates are capable of crossing cellular membranes and can directly contribute to the propagation of neurodegenerative disease pathogenesis. We propose that, once initiated, neuropathological changes might spread in a 'prion-like' manner and that disease progression is associated with the intercellular transfer of pathogenic proteins. The transfer of naked infectious particles between cells could therefore be a target for new disease-modifying therapies.

Subfields: Molecular Biology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/f520576070a56136091b084cde84e90c8ce930b8

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Citations in the corpus

Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice (2011, neutral): “Based on these and several other studies, it has been postulated that tau proteins spread in a prion-like mechanism in the tauopathies [65-67].”
The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease (2012, background): “…individuals, thereby spreading the specific neurodegenerative phenotypes distinctive to the protein being converted to the self-templating form (Brundin et al., 2010; Cushman et al., 2010; Dunning et al., 2011; Goedert et al., 2010; Polymenidou and Cleveland, 2011; Prusiner, 1984; Walker et…”
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis (2019, background): “, can exhibit prion-like behavior both in vitro and in the disease models (Brundin et al., 2010; Hock and Polymenidou, 2016).”
α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. (2011, positive): “Thus, hyperphosphorylated Tau inclusions might spread via cell-to-cell transfer and trigger nucleation/aggregation in Alzheimer disease and other tauopathies (16).”
Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders (2011, background): “These studies, along with those of Ab and tau (above), imply that disease agents can be disseminated by cells, but the means whereby protein aggregates travel between cells, and the cellular domain(s) in which the templated conversion occurs, remain poorly understood.(39,43,44,87) In vitro, aggregat”
Liquid-liquid phase separation in biology. (2014, background): “Indeed, many diseases of the brain are characterized by toxic aggregates, such as amyloid formations in Alzheimer’s disease (Brundin et al. 2010), synuclein plaques in Parkinson’s disease (Shulman et al. 2011), or plaques seen in amyotrophic lateral sclerosis (Robberecht & Philipps 2013).”
Predicting regional neurodegeneration from the healthy brain functional connectome. (2012, background): “Providing a more parsimonious account, growing evidence suggests that prion-like mechanisms may promote the spread of toxic, misfolded, nonprion protein species between interconnected neurons (Baker et al., 1993, 1994; Brundin et al., 2010; Clavaguera et al., 2009; Frost and Diamond, 2010; Frost et ”
Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences (2012, neutral): “A striking feature of a -synuclein is its transmissibility to neighbouring cells (reviewed in Brundin et al , 2010; Frost and Diamond, 2010; Steiner et al , 2011; and Hansen and Li, 2012).”