ArticleActa neuropathologica2018
Changes in proteome solubility indicate widespread proteostatic disruption in mouse models of neurodegenerative disease.
Article in Acta neuropathologica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Shift of the insoluble content of the proteome in the aging mouse brain.Proceedings of the National Academy of Sciences of the United States of America · 2023Pooled it
- Impaired Aggrephagy, Interrupted Vesicular Trafficking, and Cellular Stress, Lead to Protein Aggregation, and Synaptic Dysfunction in Cerebellum of Children and Adults with Idiopathic Autism.Cerebellum (London, England) · 2025Article
- Review
- Identification of phosphorylated tau protein interactors in progressive supranuclear palsy (PSP) reveals networks involved in protein degradation, stress response, cytoskeletal dynamics, metabolic processes, and neurotransmission.Journal of neurochemistry · 2023Article
- Myelin in Alzheimer's disease: culprit or bystander?Acta neuropathologica communications · 2023Review
- Protection against Aβ-induced neuronal damage by KU-32: PDHK1 inhibition as important target.Frontiers in aging neuroscience · 2023Article
- Isolation of Detergent Insoluble Proteins from Mouse Brain Tissue for Quantitative Analysis Using Data Independent Acquisition (DIA).Methods in molecular biology (Clifton, N.J.) · 2022Article
- Relation between Alpha-Synuclein and Core CSF Biomarkers of Alzheimer's Disease.Medicina (Kaunas, Lithuania) · 2021Article
- Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy.International journal of molecular sciences · 2021Article
- 4E-BP1 Protects Neurons from Misfolded Protein Stress and Parkinson's Disease Toxicity by Inducing the Mitochondrial Unfolded Protein Response.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Diverse proteins aggregate in mild cognitive impairment and Alzheimer's disease brain.Alzheimer's research & therapy · 2020Article
- Diversity in Aβ deposit morphology and secondary proteome insolubility across models of Alzheimer-type amyloidosis.Acta neuropathologica communications · 2020Article
- The depletion of ubiquilin in Drosophila melanogaster disturbs neurochemical regulation to drive activity and behavioral deficits.Scientific reports · 2020Article
- Widespread remodeling of proteome solubility in response to different protein homeostasis stresses.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Hsp90 and Its Co-Chaperones in Neurodegenerative Diseases.International journal of molecular sciences · 2019Review
- Non-Proteasomal UbL-UbA Family of Proteins in Neurodegeneration.International journal of molecular sciences · 2019Review
- Tau drives translational selectivity by interacting with ribosomal proteins.Acta neuropathologica · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The deposition of pathologic misfolded proteins in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia and amyotrophic lateral sclerosis is hypothesized to burden protein homeostatic (proteostatic) machinery, potentially leading to insufficient capacity to maintain the proteome. This hypothesis has been supported by previous work in our laboratory, as evidenced by the perturbation of cytosolic protein solubility in response to amyloid plaques in a mouse model of Alzheimer's amyloidosis. In the current study, we demonstrate changes in proteome solubility are a common pathology to mouse models of neurodegenerative disease. Pathological accumulations of misfolded tau, α-synuclein and mutant superoxide dismutase 1 in CNS tissues of transgenic mice were associated with changes in the solubility of hundreds of CNS proteins in each model. We observed that changes in proteome solubility were progressive and, using the rTg4510 model of inducible tau pathology, demonstrated that these changes were dependent upon sustained expression of the primary pathologic protein. In all of the models examined, changes in proteome solubility were robust, easily detected, and provided a sensitive indicator of proteostatic disruption. Interestingly, a subset of the proteins that display a shift towards insolubility were common between these different models, suggesting that a specific subset of the proteome is vulnerable to proteostatic disruption. Overall, our data suggest that neurodegenerative proteinopathies modeled in mice impose a burden on the proteostatic network that diminishes the ability of neural cells to prevent aberrant conformational changes that alter the solubility of hundreds of abundant cellular proteins.
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