ArticleCell death & disease2018
SIRT1 activation with neuroheal is neuroprotective but SIRT2 inhibition with AK7 is detrimental for disconnected motoneurons.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Neuroprotection and immunomodulation after treatment with NeuroBoost and NeuroHeal following ventral root crush in mice.IBRO neuroscience reports · 2026Article
- Diet-Driven Microglial Activation: Region-Specific Neuroinflammation in the Mouse Brain.Brain sciences · 2025Article
- Caloric Restriction Attenuated Nerve Damages Mediated Through SIRT-1-a Study Using Nerve Crush Injury Model in Rats.Molecular neurobiology · 2025Article
- Mito-TEMPO Mitigates Fibromyalgia Induced by Reserpine in Rats: Orchestration Between SIRT1, Mitochondrial Dynamics, Endoplasmic Reticulum and miRNA-320.Neurochemical research · 2025Article
- INHIBITING SIRT2 ATTENUATES SEPSIS-INDUCED ACUTE KIDNEY INJURY VIA FOXO1 ACETYLATION-MEDIATED AUTOPHAGY ACTIVATION.Shock (Augusta, Ga.) · 2025Article
- Melatonin Enhanced Microglia M2 Polarization in Rat Model of Neuro-inflammation Via Regulating ER Stress/PPARδ/SIRT1 Signaling Axis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- T-type voltage-gated channels, NaCell communication and signaling : CCS · 2024Article
- A circular network of purine metabolism as coregulators of dilated cardiomyopathy.Journal of translational medicine · 2022Article
- Bortezomib-Induced Epigenetic Alterations in Nerve Cells: Focus on the Mechanisms Contributing to the Peripheral Neuropathy Development.International journal of molecular sciences · 2022Article
- Sirtuins functions in central nervous system cells under neurological disorders.Frontiers in physiology · 2022Review
- Melatonin promotes sirtuin 1 expression and inhibits IRE1α-XBP1S-CHOP to reduce endoplasmic reticulum stress-mediated apoptosis in chondrocytes.Frontiers in pharmacology · 2022Article
- SIRT2 Affects Cell Proliferation and Apoptosis by Suppressing the Level of Autophagy in Renal Podocytes.Disease markers · 2022Article
- GRP78 Overexpression Triggers PINK1-IPBiomedicines · 2021Article
- Neuroprotective Effects of Sigma 1 Receptor Ligands on Motoneuron Death after Spinal Root Injury in Mice.International journal of molecular sciences · 2021Article
- Overexpression of sirtuin 2 and its association with prognosis in acute ischemic stroke patients.Journal of clinical laboratory analysis · 2021Article
- SIRT1 and SIRT2 Modulators: Potential Anti-Inflammatory Treatment for Depression?Biomolecules · 2021Review
- Review
- Article
- SIRT2 Inhibition Improves Functional Motor Recovery After Peripheral Nerve Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to exert effects opposite those of SIRT1; however, its roles in neurodegeneration and neuron response after nerve injury remain unclear. Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy. This injury induced a reduction of around half MN population within the hypoglossal nucleus by a non-apoptotic neurodegenerative process triggered by endoplasmic reticulum (ER) stress that resulted in activation of the unfolded protein response mediated by IRE1α and XBP1 by 21 days post injury. Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron-like cells against ER stress in vitro. In agreement with the in vitro results, NeuroHeal treatment or SIRT1 overexpression was neuroprotective of axotomized hypoglossal MNs in a transgenic mouse model. In contrast, AK7 treatment or SIRT2 genetic depletion in mice inhibited damaged MN survival. To resolve the in vitro/in vivo discrepancies, we used an organotypic spinal cord culture system that preserves glial cells. In this system, AK7 treatment of ER-stressed organotypic cultures was detrimental for MNs and increased microglial nuclear factor-κB and the consequent transcription of cytotoxic pro-inflammatory factors similarly. The results highlight the importance of glial cells in determining the neuroprotective impact of any treatment.
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