Prion-like Mechanisms in Neurodegenerative Diseases

By Bess Frost, M. Diamond. Nature Reviews Neuroscience, 2009

772 citations recorded by the source corpus.

Many non-infectious neurodegenerative diseases are associated with the accumulation of fibrillar proteins. These diseases all exhibit features that are reminiscent of those of prionopathies, including phenotypic diversity and the propagation of pathology. Furthermore, emerging studies of amyloid-β, α-synuclein and tau — proteins implicated in common neurodegenerative diseases — suggest that they share key biophysical and biochemical characteristics with prions. Propagation of protein misfolding in these diseases may therefore occur through mechanisms similar to those that underlie prion pathogenesis. If this hypothesis is verified in vivo, it will suggest new therapeutic strategies to block propagation of protein misfolding throughout the brain.

Subfields: Molecular Biology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/ba29ca814e80e4268a9e72c0ae27435e7201c4cc

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Citations in the corpus

Amyloid-β and tau — a toxic pas de deux in Alzheimer's disease (2011, background): “Substantial progress has been made more recently in understanding pathogenic mechanisms, such as the spreading of tau (and other proteins with toxic properties) between neurons and across brain regions (reviewed in Ref”
Stress granules as crucibles of ALS pathogenesis (2013, background): “It involves the transmission or propagation of protein aggregates from cell to cell and from one brain region to another during the onset and progression of disease (Aguzzi and Rajendran, 2009; Cushman et al., 2010; Frost and Diamond, 2010).”
The role of the posterior cingulate cortex in cognition and disease. (2014, background): “Proteins such as amyloid-b and TDP-43 that are causatively linked to neurodegeneration have been shown to spread trans-synaptically in their abnormal form (Frost and Diamond, 2010).”
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).”
A Network Diffusion Model of Disease Progression in Dementia (2012, positive): “These findings suggest a ‘‘prionlike’’ mechanism of transmission underlying all dementias (Frost and Diamond, 2010).”
Missing pieces in the Parkinson's disease puzzle (2010, background): “Interestingly, secretion of both monomeric and aggregated α-synuclein is elevated in response to proteasomal and mitochondrial dysfunction, cellular defects found in Parkinson's diseas”
Brain-Gut-Microbiota Axis in Alzheimer’s Disease (2019, background): “The process may spread across neuronal network via synapses.(71) Propagation of the misfolded tau protein from”
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].”
Networks of anatomical covariance (2013, background): “This diffusion model is supported by neuropathological evidence for “prion-like” trans-synaptic transmission of misfolded tau and beta amyloid (Frost and Diamond, 2010).”
Distinct tau prion strains propagate in cells and mice and define different tauopathies (2014, background): “Recently, however, experimental work on diverse amyloids has generated new interest (Frost and Diamond, 2010; Guo and Lee, 2014).”
Autophagy gone awry in neurodegenerative diseases (2010, neutral): “Similar interactions with the endocytic system have been proposed for other pathogenic proteins, such as amyloid-β, α-synuclein and tau proteins, involved in noninfectious neurodegenerative disorder”
Linking Lipids to Alzheimer’s Disease: Cholesterol and Beyond (2011, background): “Finally, a growing scientific community is investigating the mechanisms through which tau aggregates may be secreted or exert their prion-like infectious properties across cell membranes, thus propagating the tau patholog”
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 ”
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”
Impairment of Glymphatic Pathway Function Promotes Tau Pathology after Traumatic Brain Injury (2014, background): “Emerging evidence suggests that the movement of tau and tau aggregates through the extracellular space plays an important role in the development and spread of intracellular tau pathology (Frost and Diamond, 2010; Jucker and Walker, 2011; Walker et al., 2013).”