The DOI matches its Crossref record; 174 of the 174 references it cites were found in a registry or an index.
Intercellular Spread of Protein Aggregates in Neurodegenerative Disease
Open accessAbstract
Most neurodegenerative diseases are characterized by the accumulation of protein aggregates, some of which are toxic to cells. Mounting evidence demonstrates that in several diseases, protein aggregates can pass from neuron to neuron along connected networks, although the role of this spreading phenomenon in disease pathogenesis is not completely understood. Here we briefly review the molecular and histopathological features of protein aggregation in neurodegenerative disease, we summarize the evidence for release of proteins from donor cells into the extracellular space, and we highlight some other mechanisms by which protein aggregates might be transmitted to recipient cells. We also discuss the evidence that supports a role for spreading of protein aggregates in neurodegenerative disease pathogenesis and some limitations of this model. Finally, we consider potential therapeutic strategies to target spreading of protein aggregates in the treatment of neurodegenerative diseases.
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In the citing paper
“while proteins involved in neurodegenerative diseases may normally be either intracellular or extracellular in nature, all are present in the extracellular space.”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [76]
In the citing paper
“Sampling of CSF and extracellular fluid have documented that amyloid-ß, tau and a-synuclein are all present outside the cytosol.”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [76]
In the citing paper
“These proteins all lack N-terminal signal sequences, so that unconventional mechanisms must be responsible for their release (76).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [76]
In the citing paper
“While seemingly a cell-intrinsic phenomenon, one of the curious features of the pathology of these diseases is the apparent spread of the cellular abnormalities to anatomically connected brain regions.”
From Asynchronous, contagious and digital aging (2021) · cites this paper as [59]
In the citing paper
“The notion of cell-to-cell spreading of cellular dysfunction is of course not limited to the biology of senescence. This is becoming an increasingly recognized phenomenon in the pathogenesis of neurodegenerative diseases.59”
From Asynchronous, contagious and digital aging (2021) · cites this paper as [59]
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Glymphatic failure as a final common pathway to dementia
Nedergaard, M., & Goldman, S. A. (2020) · Science · doi:10.1126/science.abb8739 · Cited by 1,145
Exercise sustains the hallmarks of health
Qiu, Y., Fernández-García, B., Lehmann, H. I., Li, G., Kroemer, G., López-Otín, C., & Xiao, J. (2023) · Journal of Sport and Health Science · doi:10.1016/j.jshs.2022.10.003 · Cited by 270
Amyloid-type Protein Aggregation and Prion-like Properties of Amyloids
Willbold, D., Strodel, B., Schroeder, G. F., Hoyer, W., & Heise, H. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00196 · Cited by 226
Dural lymphatics regulate clearance of extracellular tau from the CNS
Patel, T. K., Habimana-Griffin, L., Gao, X., Xu, B. J., Achilefu, S., Alitalo, K. K., McKee, C. A., Sheehan, P. W., Musiek, E. S., Xiong, C., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0312-x · Cited by 220
Self-citationConformational strains of pathogenic amyloid proteins in neurodegenerative diseases
Li, D., & Liu, C. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00603-7 · Cited by 124
Metadata
- Authors
- Davis, A. A., Leyns, C. E. G., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Annual Review of Cell and Developmental Biology
- Publisher
- Annual Reviews
- Published
- 2018-10-06
- Volume
- 34
- Issue
- 1
- Pages
- 545-568
- ISSN
- 1081-0706 (ISSN-L)
- 1530-8995
- PMC
- PMC6350082
- OpenAlex
- W2883506729
- Cited by
- 131
- References
- 174
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 14 · 2023: 16 · 2022: 24 · 2021: 20 · 2020: 20 · 2019: 13 · 2018: 2
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (K08NS101118)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- protein aggregates, neurodegenerative diseases, intercellular spread, prion-like propagation, extracellular protein release, treatment options, neurodegeneration
- MeSH terms
- Chronic Traumatic Encephalopathy, Alzheimer Disease, Amyotrophic Lateral Sclerosis, Humans, Huntington Disease, Neurons, Parkinson Disease, Prion Diseases, Neurodegenerative Diseases, Frontotemporal Dementia, Protein Aggregation, Pathological, Protein Aggregates
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