ArticleFrontiers in molecular neuroscience2022
Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points.
Article in Frontiers in molecular neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Mapping the Synaptome in Neurodegeneration: Emerging Clinical Applications of SV2A PET Imaging.Molecular diagnosis & therapy · 2026Article
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- The Protonic Brain: Nanoscale pH Dynamics, Proton Wires, and Acid-Base Information Coding in Neural Tissue.International journal of molecular sciences · 2026Review
- Aging Rewires Neuronal Metabolism, Exacerbating Cell Death After Ischemic Stroke: A Hidden Reason for the Failure of Neuroprotection.International journal of molecular sciences · 2025Article
- Mitochondrial-specific perturbation of Drosophila RNase Z in neurons leads to motor impairments, disrupted learning and neurodegeneration.PLoS genetics · 2025Article
- Peripheral sequestration of huntingtin delays neuronal death and depends on N-terminal ubiquitination.Communications biology · 2024Article
- A clinical study onAvicenna journal of phytomedicineArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synaptic integrity and function depend on myriad proteins - labile molecules with finite lifetimes that need to be continually replaced with freshly synthesized copies. Here we describe experiments designed to expose synaptic (and neuronal) properties and functions that are particularly sensitive to disruptions in protein supply, identify proteins lost early upon such disruptions, and uncover potential, yet currently underappreciated failure points. We report here that acute suppressions of protein synthesis are followed within hours by reductions in spontaneous network activity levels, impaired oxidative phosphorylation and mitochondrial function, and, importantly, destabilization and loss of both excitatory and inhibitory postsynaptic specializations. Conversely, gross impairments in presynaptic vesicle recycling occur over longer time scales (days), as does overt cell death. Proteomic analysis identified groups of potentially essential 'early-lost' proteins including regulators of synapse stability, proteins related to bioenergetics, fatty acid and lipid metabolism, and, unexpectedly, numerous proteins involved in Alzheimer's disease pathology and amyloid beta processing. Collectively, these findings point to neuronal excitability, energy supply and synaptic stability as early-occurring failure points under conditions of compromised supply of newly synthesized protein copies.
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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 Socratic graph.