ArticleProceedings of the National Academy of Sciences of the United States of America2016
The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- ProSAAS overexpression arrests progression of motor deficits in a rat alpha-synuclein model of Parkinson's disease.Translational neurodegeneration · 2026Article
- Integrated Aerobic Exercise and Multisensory Environment Training for Age-related Cognitive Decline via Hippocampal-prefrontal Neural Circuit Modulation.Molecular neurobiology · 2025Article
- ProSAAS neuropeptides and receptors GPR171 and GPR83: Potential therapeutic applications for pain, anxiety, and body weight regulation.The Journal of pharmacology and experimental therapeutics · 2025Review
- PCSK1N as a Tumor Size Marker and an ER Stress Response Protein in Corticotroph Pituitary Adenomas.The Journal of clinical endocrinology and metabolism · 2025Article
- Article
- Mechanisms of Transsynaptic Degeneration in the Aging Brain.Aging and disease · 2024Review
- ProSAAS is preferentially up-regulated during homeostatic scaling and reduces amyloid plaque burden in the 5xFAD mouse hippocampus.Journal of neurochemistry · 2024Article
- ProSAAS is Preferentially Secreted from Neurons During Homeostatic Scaling and Reduces Amyloid Plaque Size in the 5xFAD Mouse Hippocampus.bioRxiv : the preprint server for biology · 2024Article
- Article
- Extracellular protein homeostasis in neurodegenerative diseases.Nature reviews. Neurology · 2023Review
- Extracellular chaperone networks and the export of J-domain proteins.The Journal of biological chemistry · 2023Review
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Review
- Synaptic proteomics reveal distinct molecular signatures of cognitive change and C9ORF72 repeat expansion in the human ALS cortex.Acta neuropathologica communications · 2022Article
- Sequestration of TDP-43ACS chemical neuroscience · 2022Article
- A Novel 16-Genes Signature Scoring System as Prognostic Model to Evaluate Survival Risk in Patients with Glioblastoma.Biomedicines · 2022Article
- The proSAAS Chaperone Provides Neuroprotection and Attenuates Transsynaptic α-Synuclein Spread in Rodent Models of Parkinson's Disease.Journal of Parkinson's disease · 2022Article
- Age-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction.Molecular therapy. Nucleic acids · 2021Article
- Small molecule inhibitors of α-synuclein oligomers identified by targeting early dopamine-mediated motor impairment in C. elegans.Molecular neurodegeneration · 2021Article
- Extracellular protein components of amyloid plaques and their roles in Alzheimer's disease pathology.Molecular neurodegeneration · 2021Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Emerging evidence strongly suggests that chaperone proteins are cytoprotective in neurodegenerative proteinopathies involving protein aggregation; for example, in the accumulation of aggregated α-synuclein into the Lewy bodies present in Parkinson's disease. Of the various chaperones known to be associated with neurodegenerative disease, the small secretory chaperone known as proSAAS (named after four residues in the amino terminal region) has many attractive properties. We show here that proSAAS, widely expressed in neurons throughout the brain, is associated with aggregated synuclein deposits in the substantia nigra of patients with Parkinson's disease. Recombinant proSAAS potently inhibits the fibrillation of α-synuclein in an in vitro assay; residues 158-180, containing a largely conserved element, are critical to this bioactivity. ProSAAS also exhibits a neuroprotective function; proSAAS-encoding lentivirus blocks α-synuclein-induced cytotoxicity in primary cultures of nigral dopaminergic neurons, and recombinant proSAAS blocks α-synuclein-induced cytotoxicity in SH-SY5Y cells. Four independent proteomics studies have previously identified proSAAS as a potential cerebrospinal fluid biomarker in various neurodegenerative diseases. Coupled with prior work showing that proSAAS blocks β-amyloid aggregation into fibrils, this study supports the idea that neuronal proSAAS plays an important role in proteostatic processes. ProSAAS thus represents a possible therapeutic target in neurodegenerative disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.