ArticleNeuropathology and applied neurobiology2020
Expression of p16 and p21 in the frontal association cortex of ALS/MND brains suggests neuronal cell cycle dysregulation and astrocyte senescence in early stages of the disease.
Article in Neuropathology and applied neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 78 citations in OpenAlex.
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- Senescence Markers and Associated Transcriptomic Changes Are Expressed at Early Stages of Alzheimer's Neuropathology but Are Not Independently Related to Dementia.International journal of molecular sciences · 2026Article
- Senolytic Therapy as a Preventive Strategy for Spine Degeneration and Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Viral Mimicry of Alzheimer's Disease: Innate Sensing of Self-Nucleic Acids as a Driver of Glial Senescence.Journal of molecular neuroscience : MN · 2026Review
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- Aberrant CDK4/6-driven cell-cycle reentry drives neuronal loss and defines a therapeutic target in C9orf72 ALS/FTD.iScience · 2026Article
- From Neuron-Centric to Glia-Centric: How Aging Glial Networks Drive Neurodegenerative Disease.Journal of neurochemistry · 2026Review
- NOR1 loss relates to inflammation and biological ageing in multiple sclerosis motor cortex.Brain communications · 2026Article
- Senolytics as Modulators of Critical Signaling Pathways: a Promising Strategy to Combat Brain Aging and Neurodegenerative Disorders.Molecular neurobiology · 2025Review
- Telomerase Depletion Accelerates Ageing of the Zebrafish Brain.Aging cell · 2025Article
- Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.Translational neurodegeneration · 2025Review
- Unleashing endogenous regeneration by senolytics.Journal of translational medicine · 2025Review
- Interplay Between Aging and Glial Cell Dysfunction: Implications for CNS Health.Life (Basel, Switzerland) · 2025Review
- Δ133p53α-mediated inhibition of astrocyte senescence and neurotoxicity as a possible therapeutic approach for neurodegenerative diseases.Neuroscience · 2025Review
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- Targeting Cellular Senescence: Pathophysiology in Multisystem Age-Related Diseases.Biomedicines · 2025Review
- SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes.Life science alliance · 2025Article
- Aging-dependent YAP1 reduction contributes to AD pathology by upregulating the Nr4a1-AKT/GSK-3β axis.Translational neurodegeneration · 2025Article
- Senolytic treatment for low back pain.Science advances · 2025Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
aimsCellular senescence plays a role in organismal ageing and has been linked to persistent DNA damage in age-related diseases. Brain senescence has been described in astrocytes and microglia, but it is less well understood in neurones. Evidence suggests that neurones activate a senescence-like mechanism that could contribute to neurodegeneration. We aimed to determine whether a persistent DNA damage response (DDR) and senescence activation are features of motor neurone disease (amyotrophic lateral sclerosis, ALS/MND).
methodsWe examined expression of senescence (p16 and p21) and DNA damage markers (8-OHdG and γH2AX) in motor cortex (MCx), frontal association cortex (FACx) and occipital cortex (OCx) in post-mortem tissue donated by patients with ALS/MND and controls.
resultsNuclear expression of p16 and p21 was detected in glial cells; double immunofluorescence for p16/p21 and glial fibrillary acidic protein (GFAP) suggested that some of these cells were GFAP
conclusionsExpression of p16 and p21 in glia, mainly in astrocytes, suggests senescence induction in these cells; however, neuronal p21 expression might reflect a more general mechanism of age-related cell cycle dysregulation. The significantly higher proportion of cells expressing either p16 or p21 in the FACx of ALS/MND donors could indicate senescence activation and cell cycle dysregulation in early stages of the disease.
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