ArticleAging cell2023
Necroptosis inhibition counteracts neurodegeneration, memory decline, and key hallmarks of aging, promoting brain rejuvenation.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Targeting non-apoptotic regulated cell death (RCD) to treat neurodegenerative diseases.Acta pharmaceutica Sinica. B · 2026Review
- The RIPK3 Inhibitor GSK872 Attenuates Inflammation and Necroptosis via Modulation of the JNK Signaling Pathway in LPS-Stimulated Microglia.Biomolecules & therapeutics · 2026Article
- TMAO Induced Kidney Aging by Activating ZBP1-Mediated Necroptosis.Physiological research · 2026Article
- Unraveling sex differences in age-related hippocampal decline: differential mitochondrial dysfunction, Lonp1-dependent mitochondrial proteostasis and mtROS production in aged C57BL/6 mice.Cell death & disease · 2025Article
- Acute Administration of Edaravone Improves Cognitive Impairment in a Mouse Model of mPFC Ischemia: Crosstalk Between Necroptosis, Neuroinflammation, and Antioxidant Defense.Molecular neurobiology · 2025Article
- Advances in the Study of Necroptosis in Vascular Dementia: Focus on Blood-Brain Barrier and Neuroinflammation.CNS neuroscience & therapeutics · 2025Review
- Mef2c Exacerbates Neuron Necroptosis via Modulating Alternative Splicing of Cflar in Ischemic Stroke With Hyperlipidemia.CNS neuroscience & therapeutics · 2024Article
- Osteocyte ferroptosis induced by ATF3/TFR1 contributes to cortical bone loss during ageing.Cell proliferation · 2024Article
- MLKL overexpression leads to CaCell calcium · 2024Article
- Regulated cell death and its role in Alzheimer's disease and amyotrophic lateral sclerosis.Acta neuropathologica · 2024Review
- RIP3 in Necroptosis: Underlying Contributions to Traumatic Brain Injury.Neurochemical research · 2024Review
- Necroptosis inhibition counteracts neurodegeneration, memory decline, and key hallmarks of aging, promoting brain rejuvenation.Aging cell · 2023Article
- RIP kinases and necroptosis in aging and aging-related diseases.Life medicine · 2022Review
- The Second Euro Geroscience Conference: Highlights of the Current Advances and Challenges in the Field of Geroscience.The journal of nutrition, health & aging · 2022Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Age is the main risk factor for the development of neurodegenerative diseases. In the aged brain, axonal degeneration is an early pathological event, preceding neuronal dysfunction, and cognitive disabilities in humans, primates, rodents, and invertebrates. Necroptosis mediates degeneration of injured axons, but whether necroptosis triggers neurodegeneration and cognitive impairment along aging is unknown. Here, we show that the loss of the necroptotic effector Mlkl was sufficient to delay age-associated axonal degeneration and neuroinflammation, protecting against decreased synaptic transmission and memory decline in aged mice. Moreover, short-term pharmacologic inhibition of necroptosis targeting RIPK3 in aged mice, reverted structural and functional hippocampal impairment, both at the electrophysiological and behavioral level. Finally, a quantitative proteomic analysis revealed that necroptosis inhibition leads to an overall improvement of the aged hippocampal proteome, including a subclass of molecular biofunctions associated with brain rejuvenation, such as long-term potentiation and synaptic plasticity. Our results demonstrate that necroptosis contributes to age-dependent brain degeneration, disturbing hippocampal neuronal connectivity, and cognitive function. Therefore, necroptosis inhibition constitutes a potential geroprotective strategy to treat age-related disabilities associated with memory impairment and cognitive decline.
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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.