ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Melatonin Induction of APP Intracellular Domain 50 SUMOylation Alleviates AD through Enhanced Transcriptional Activation and Aβ Degradation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases.Molecular neurobiology · 2023Pooled it
- PIAS1-mediated GSK3β SUMOylation exacerbates tauopathy and cognitive deficits in Alzheimer's disease models.Molecular psychiatry · 2026Article
- SUMOylation in Mitochondrial Quality Control: Mechanisms and Implications for Neurodegenerative Disease.Molecular neurobiology · 2026Review
- E3 ubiquitin ligases: structural diversity, dysregulation in disease, and their emerging role in targeted therapeutic strategies.Frontiers in molecular biosciences · 2026Review
- Neprilysin regulates the progression of glioblastoma: an in-vitro study using siRNA mediated gene silencing and HDAC1 mediated upregulation of neprilysin in U87 MG cells.Molecular and cellular biochemistry · 2025Article
- APP SUMOylation prevents BACE1 cleavage of APP and increases BACE1 degradation to promote the nonamyloidogenic pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- APP lysine 612 lactylation ameliorates amyloid pathology and memory decline in Alzheimer's disease.The Journal of clinical investigation · 2025Article
- Development and characterization of the mode-of-action of inhibitory and agonist peptides targeting the voltage-gated sodium channel SCN1B beta-subunit.Journal of molecular and cellular cardiology · 2024Article
- Protein modification in neurodegenerative diseases.MedComm · 2024Review
- Novel role of NCoR1 in impairing spatial memory through the mediation of a novel interacting protein DEC2.Cellular and molecular life sciences : CMLS · 2024Article
- Protective Effect of the Novel Melatonin Analogue Containing Donepezil Fragment on Memory Impairment via MT/ERK/CREB Signaling in the Hippocampus in a Rat Model of Pinealectomy and Subsequent AβInternational journal of molecular sciences · 2024Article
- MicroRNA biomarkers as next-generation diagnostic tools for neurodegenerative diseases: a comprehensive review.Frontiers in molecular neuroscience · 2024Review
- Paradoxes of Cellular SUMOylation Regulation: A Role of Biomolecular Condensates?Pharmacological reviews · 2023Review
- The Involvement of Post-Translational Modifications in Regulating the Development and Progression of Alzheimer's Disease.Molecular neurobiology · 2023Review
- Review
- Whole-exome sequencing detected a novel APP variant in a Han-Chinese family with Alzheimer's disease.Molecular biology reports · 2023Article
- Article
- Therapeutic role of yoga in neuropsychological disorders.World journal of psychiatry · 2021Review
- Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders.Antioxidants (Basel, Switzerland) · 2021Review
- Looking at Alzheimer's Disease Pathogenesis from the Nuclear Side.Biomolecules · 2021Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid precursor protein (APP) intracellular domain (AICD) is implicated in the pathogenesis of Alzheimer's disease (AD), but post-translational modification of AICD has rarely been studied and its role in AD is unknown. In this study, we examined the role and molecular mechanism of AICD SUMOylation in the pathogenesis of AD. We found that AICD is SUMO-modified by the SUMO E3 ligase protein inhibitor of activated STAT1 (PIAS1) in the hippocampus at Lys-43 predominantly, and that knockdown of PIAS1 decreases endogenous AICD SUMOylation. AICD SUMOylation increases AICD association with its binding protein Fe65 and increases AICD nuclear translocation. Furthermore, AICD SUMOylation increases AICD association with cyclic AMP-responsive element binding protein (CREB) and p65 and their DNA binding for transcriptional activation of neprilysin (NEP) and transthyretin (TTR), two major Aβ-degrading enzymes, respectively. Consequently, AICD SUMOylation decreases the Aβ level, Aβ oligomerization, and amyloid plaque deposits. It also rescues spatial memory deficits in APP/PS1 mice. Conversely, blockade of AICD SUMOylation at Lys-43 produces the opposite effects. Melatonin is identified as an endogenous stimulus that induces AICD SUMOylation. It also decreases the Aβ level and rescues reduction of PIAS1, NEP, and TTR expression in APP/PS1 mice. In this study, we demonstrate that AICD SUMOylation functions as a novel endogenous defense mechanism to combat AD.
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