ArticleAutophagy2022
Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders.
Article in Autophagy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
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- Integrative transcriptomics and electrophysiological profiling of hiPSC-derived neurons identifies novel druggable pathways in Koolen-de Vries Syndrome.Molecular psychiatry · 2026Article
- Hierarchical Afferent Connectivity Drives Population-Wide Bursting Dynamics in a Computational Model of Human-Derived Excitatory Neuronal Networks.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Maternal exposure to low-dose tartrazine during lactation induces neurotoxicity in rat pups through oxidative stress, endoplasmic reticulum stress, and autophagy suppression.Anatomy & cell biology · 2026Article
- Loss of function of the chromatin remodeling geneProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Human neuronal networks on micro-electrode arrays as a tool to assess genotype-phenotype correlation in CACNA1A-related disorders.Stem cell reports · 2026Article
- Characterizing the Pleiotropic Architecture of Impulsivity and Its Links to Psychopathology and Neurodevelopment.The American journal of psychiatry · 2026Article
- Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.Molecular psychiatry · 2026Article
- Improving variant interpretation and diagnosis in Koolen-de Vries syndrome through a curated genotype-phenotype repository.Molecular genetics and genomics : MGG · 2025Article
- The multifaceted role of SQSTM1/p62 in disc degeneration: A master regulator of cellular stress responses.Biochemistry and biophysics reports · 2025Review
- Evolutionary hotspots of structural variation drive inter-individual differences in the expression of fusion transcripts in the human brain.Nucleic acids research · 2025Article
- Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.Research square · 2025Article
- Multifactorial etiology of progressive supranuclear palsy (PSP): the genetic component.Acta neuropathologica · 2025Review
- Multi-omics study reveals differential expression and phosphorylation of autophagy-related proteins in autism spectrum disorder.Scientific reports · 2025Article
- PLK3 weakens antioxidant defense and inhibits proliferation of porcine Leydig cells under oxidative stress.Scientific reports · 2025Article
- Characterisation of the function of a lncRNA containing SINE-VNTR-Alu 67 to regulate the genes at theExperimental biology and medicine (Maywood, N.J.) · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Decoding brain aging trajectory: predictive discrepancies, genetic susceptibilities, and emerging therapeutic strategies.Frontiers in aging neuroscience · 2025Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macroautophagy (hereafter referred to as autophagy) is a finely tuned process of programmed degradation and recycling of proteins and cellular components, which is crucial in neuronal function and synaptic integrity. Mounting evidence implicates chromatin remodeling in fine-tuning autophagy pathways. However, this epigenetic regulation is poorly understood in neurons. Here, we investigate the role in autophagy of KANSL1, a member of the nonspecific lethal complex, which acetylates histone H4 on lysine 16 (H4K16ac) to facilitate transcriptional activation. Loss-of-function of KANSL1 is strongly associated with the neurodevelopmental disorder Koolen-de Vries Syndrome (KdVS). Starting from KANSL1-deficient human induced-pluripotent stem cells, both from KdVS patients and genome-edited lines, we identified SOD1 (superoxide dismutase 1), an antioxidant enzyme, to be significantly decreased, leading to a subsequent increase in oxidative stress and autophagosome accumulation. In KANSL1-deficient neurons, autophagosome accumulation at excitatory synapses resulted in reduced synaptic density, reduced GRIA/AMPA receptor-mediated transmission and impaired neuronal network activity. Furthermore, we found that increased oxidative stress-mediated autophagosome accumulation leads to increased MTOR activation and decreased lysosome function, further preventing the clearing of autophagosomes. Finally, by pharmacologically reducing oxidative stress, we could rescue the aberrant autophagosome formation as well as synaptic and neuronal network activity in KANSL1-deficient neurons. Our findings thus point toward an important relation between oxidative stress-induced autophagy and synapse function, and demonstrate the importance of H4K16ac-mediated changes in chromatin structure to balance reactive oxygen species- and MTOR-dependent autophagy.
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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.