ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
The development of ADAM10 endocytosis inhibitors for the treatment of Alzheimer's disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- The calcium channel blocker diltiazem ameliorates parthanatos in juvenile neuronal ceroid lipofuscinosis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Loss of Atp8a2 drives neurodegeneration through the dysregulation of spatiotemporal phosphatidylserine externalization in mature neurons.Cell death & disease · 2026Article
- Review
- USP18 Impacts Cisplatin Resistance in Ovarian Cancer Cells by Modulating DNA Repair.International journal of biological sciences · 2026Article
- Synapse vulnerability and resilience across the clinical spectrum of dementias.Nature reviews. Neurology · 2025Review
- Acute targeting of N-terminal tau protein has long-lasting beneficial effects in Tg2576 APP/Aβ mouse model by reducing cognitive impairment, cerebral Aβ-amyloidosis, synaptic remodeling and microgliosis later in life.Acta neuropathologica communications · 2025Article
- Cognitive function and retinal biomarkers as novel approach to diagnosing and assessing autism spectrum disorder.Scientific reports · 2025Article
- mTOR signaling and Alzheimer's disease: What we know and where we are?CNS neuroscience & therapeutics · 2024Review
- Systematic druggable genome-wide Mendelian randomisation identifies therapeutic targets for Alzheimer's disease.Journal of neurology, neurosurgery, and psychiatry · 2023Article
- Novel therapeutic approaches to target neurodegeneration.British journal of pharmacology · 2023Review
- Article
- Therapeutic potential of ADAM10 modulation in Alzheimer's disease: a review of the current evidence.Cell communication and signaling : CCS · 2023Review
- HMGB1 mediates synaptic loss and cognitive impairment in an animal model of sepsis-associated encephalopathy.Journal of neuroinflammation · 2023Article
- Upregulation of sFRP1 Is More Profound in Female than Male 5xFAD Mice and Positively Associated with Amyloid Pathology.Journal of Alzheimer's disease : JAD · 2023Article
- Shifting the balance: soluble ADAM10 as a potential treatment for Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- The Strategies for Treating "Alzheimer's Disease": Insulin Signaling May Be a Feasible Target.Current issues in molecular biology · 2022Review
- The role of ADAM10 in astrocytes: Implications for Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of new therapeutic avenues that target the early stages of Alzheimer's disease (AD) is urgently necessary. A disintegrin and metalloproteinase domain 10 (ADAM10) is a sheddase that is involved in dendritic spine shaping and limits the generation of amyloid-β. ADAM10 endocytosis increases in the hippocampus of AD patients, resulting in the decreased postsynaptic localization of the enzyme. To restore this altered pathway, we developed a cell-permeable peptide (PEP3) with a strong safety profile that is able to interfere with ADAM10 endocytosis, upregulating the postsynaptic localization and activity of ADAM10. After extensive validation, experiments in a relevant animal model clarified the optimal timing of the treatment window. PEP3 administration was effective for the rescue of cognitive defects in APP/PS1 mice only if administered at an early disease stage. Increased ADAM10 activity promoted synaptic plasticity, as revealed by changes in the molecular compositions of synapses and the spine morphology. Even though further studies are required to evaluate efficacy and safety issues of long-term administration of PEP3, these results provide preclinical evidence to support the therapeutic potential of PEP3 in AD.
Indexed as
Identifiers
What OpenQuestion holds
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.