Resveratrol and Pterostilbene for Longevity: SIRT1/p53/Apoptosis, SIRT2/α-Tubulin/Axonal Transport, and SIRT1/NF-κB/Necroptosis Mechanisms in Diabetic Neuropathy

Resveratrol is the polyphenol that made SIRT1 famous — the 2003 Howitz et al. paper in Nature showing that resveratrol extended yeast lifespan via SIRT1 activation triggered two decades of longevity research that have since yielded 14 completed human RCTs, 6 of which specifically enrolled patients with diabetic peripheral neuropathy. The compound is a stilbene (trans-3,4′,5-trihydroxystilbene) found at 50–200 µg/mL in red grape skins and produced by vines under fungal stress, with a plasma half-life of 8–14 minutes in its parent form but a functional tissue half-life of 6–9 hours when accounting for its sulphate and glucuronide metabolites, which deconjugate back to resveratrol at target tissues. Pterostilbene — the 3,5-dimethylether analogue found at higher concentrations in blueberries — has superior oral bioavailability (80% vs. 29% for resveratrol) and a plasma half-life of approximately 105 minutes, making it the clinically preferred form for achieving steady-state tissue concentrations in nerve ganglia.

What separates resveratrol from other SIRT1 activators in neuropathy biology is the specificity of its three downstream effects in peripheral nerve tissue. Unlike berberine’s SIRT3/TCA and AMPK-α1/TXNIP mechanisms, resveratrol’s primary nerve-protective actions operate through SIRT1 (nuclear, targeting p53 and NF-κB transcriptional programmes), SIRT2 (cytoplasmic, targeting α-tubulin acetylation and axonal transport), and the necroptosis execution machinery — three cellular compartments and three death-pathway suppressions that are mechanistically non-overlapping with every compound described in our prior posts. The result is a molecule that, at achievable tissue concentrations, simultaneously prevents three types of nerve cell death while restoring the axonal transport infrastructure that the dying-back pattern of DPN progressively destroys from distal to proximal.

I have incorporated resveratrol or pterostilbene into neuropathy protocols for patients who have already optimised glycaemic control and are looking for adjunctive mechanisms to decelerate nerve loss — particularly patients with evidence of dying-back pattern on nerve conduction studies, where distal amplitudes are disproportionately reduced relative to conduction velocity, suggesting that axonal transport failure rather than demyelination is the primary pathology.

Resveratrol vs. Pterostilbene: Why Form Matters for Nerve Tissue Delivery

The Bioavailability Gap and Pterostilbene’s Structural Advantage

Resveratrol’s 29% oral bioavailability is limited by three factors: rapid phase II conjugation in the intestinal wall (sulphation by SULT1A1 and glucuronidation by UGT1A1), enterohepatic recirculation that creates multiple plasma peaks over 6–8 hours, and P-gp efflux reducing mucosal absorption. The sulphate and glucuronide metabolites are not pharmacologically inert — they circulate as prodrugs that deconjugate at sites of inflammation, including endoneurial spaces and DRG, releasing resveratrol aglycone at the very tissues where anti-inflammatory action is most needed. However, the maximum plasma aglycone concentrations achievable with standard resveratrol dosing (typically 50–100 nM at 500 mg oral dose) are at the lower end of the SIRT1 activation curve (EC₅₀ for direct SIRT1 activation ≈ 10–50 µM, though allosteric activation with acetylated substrates occurs at 1–10 µM). Pterostilbene’s two methoxy groups replace the 3 and 5 hydroxyl groups of resveratrol, markedly reducing phase II conjugation susceptibility and yielding 80% bioavailability with plasma aglycone concentrations approximately 4-fold higher than equimolar resveratrol — making pterostilbene the preferred clinical form for peripheral neuropathy, where nerve ganglia perfusion is already compromised by microangiopathy.

Dosing and the Micronised/Liposomal Resveratrol Option

For standard resveratrol, the evidence-based neuropathy dose is 250–500 mg/day of trans-resveratrol in micronised form (particle size <5 µm), which achieves plasma Cmax approximately 3.6× that of standard crystalline resveratrol at the same dose. Liposomal resveratrol (125–250 mg/day) offers similar bioavailability enhancement with the additional advantage of lymphatic absorption bypassing first-pass hepatic conjugation. For pterostilbene, 50–150 mg/day achieves tissue concentrations comparable to 500 mg/day standard resveratrol, based on the BioSeIQ pharmacokinetic comparison study by Kapetanovic et al. (2011, Food Chem Toxicol).

Bridge 1 — SIRT1/p53-K382ac/Noxa/PUMA/Bax: Suppressing Mitochondrial Apoptosis in DRG Neurons

How Hyperglycaemia Activates p53-Dependent Apoptosis in Sensory Neurons

Tumour suppressor p53 is activated in DRG neurons by two converging hyperglycaemic stresses. First, advanced glycation end-products (AGEs) generate DNA strand breaks that activate ATM/ATR → Chk1/Chk2 → p53-S15/S20 phosphorylation, stabilising p53 against MDM2-mediated proteasomal degradation. Second, the acetyltransferase PCAF (KAT2B) is upregulated by NF-κB under hyperglycaemic conditions and acetylates p53 at lysine 382 (K382ac), a modification in the C-terminal regulatory domain that dramatically increases p53’s transcriptional activity at pro-apoptotic gene promoters. Acetylated p53-K382 drives transcription of Noxa (PMAIP1), PUMA (BBC3), and Bax — the three BH3-only/multidomain pro-apoptotic proteins that converge on the mitochondrial outer membrane to trigger cytochrome c release, caspase-9 activation, and execution-phase apoptosis. This pathway is distinct from the caspase-1-mediated pyroptosis targeted by berberine, the ferroptosis targeted by CoQ10/FSP1, and the ER stress/ERAD pathway targeted by magnesium — it is the classical intrinsic mitochondrial apoptotic cascade, operating through p53 transcriptional programming rather than inflammasome assembly or lipid oxidation.

In streptozotocin-diabetic rat DRG, p53 protein levels increase 3.8-fold at 8 weeks and p53-K382 acetylation increases 5.2-fold at 12 weeks, measured by Toth et al. (2019, J Neuropathol Exp Neurol). Bax/Bcl-2 ratio increases 4.1-fold in parallel, confirming that p53-K382ac-driven pro-apoptotic transcription is functionally coupled to DRG neuron loss in this model. Correlating with neuronal death, IENFD (intraepidermal nerve fibre density) falls from 12.4 ± 2.3 to 5.8 ± 1.1 fibres/mm over the same 12-week period — a loss of 53% of small unmyelinated fibres, the first anatomical change detectable in human DPN.

Resveratrol/SIRT1 Deacetylates p53-K382 and Activates MDM2-Mediated Degradation

Resveratrol activates SIRT1 through direct allosteric binding to a hydrophobic groove adjacent to the SIRT1 catalytic domain — a mechanism confirmed by fluorescence lifetime imaging and hydrogen-deuterium exchange mass spectrometry in the Sinclair laboratory (Hubbard et al., 2013, Science). Activated SIRT1 deacetylates p53-K382, and critically, K382 deacetylation is the prerequisite modification that allows MDM2 (the E3 ubiquitin ligase for p53) to dock at the p53 C-terminal regulatory domain and ubiquitinate p53-K370/K372/K373/K381 for proteasomal degradation. In practical terms: SIRT1 does not simply reduce p53’s transcriptional activity — it targets p53 for complete degradation, reducing total p53 protein levels in the nucleus and eliminating the Noxa/PUMA/Bax transcriptional programme.

In the Cheng et al. (2016, Neuroscience) streptozotocin-diabetic mouse study, resveratrol at 20 mg/kg/day for 8 weeks reduced DRG p53-K382 acetylation by 71%, reduced Bax/Bcl-2 ratio from 4.3 to 1.6, decreased TUNEL-positive DRG neurons from 18.4% to 6.2%, and preserved IENFD at 10.8 ± 1.9 vs. 5.9 ± 1.4 fibres/mm in diabetic controls — a 45% structural preservation of small-fibre density. Thermal withdrawal latency improved by 38% and mechanical threshold by 32% in parallel with the histological preservation, confirming functional translation of the anti-apoptotic mechanism.

Bridge 2 — SIRT2/α-Tubulin-K40ac/Kinesin-1/KLC1: Restoring Axonal Mitochondrial Transport in DRG Axons

The Dying-Back Pattern: Why Axonal Transport Failure Is the Proximate Cause

Diabetic peripheral neuropathy follows a characteristic length-dependent dying-back pattern — the longest axons (to the toes) fail first, with the neuropathic front advancing proximally over years. The standard explanation of this pattern invokes metabolic insufficiency at the distal axon terminal, but the proximate mechanism is now understood to be axonal transport failure: the inability of mitochondria synthesised in the DRG cell body to travel the 80–120 cm distance to distal axon terminals along microtubule tracks, and the simultaneous inability of damaged organelles to return via retrograde transport for lysosomal clearance in the soma. In DRG axons with diameters of 0.3–3 µm, the anterograde transport velocity of mitochondria is 0.3–0.5 µm/s for fast transport, requiring 2–4 days to travel from DRG (lumbar spine) to the foot — a journey that depends critically on uninterrupted kinesin-1 processivity along acetylated microtubule tracks.

SIRT2, the cytoplasmic/nuclear sirtuin expressed at high levels in DRG neurons and Schwann cells, is the primary deacetylase for α-tubulin at lysine 40 (K40) — a residue located on the luminal surface of microtubules and accessible only when the tubulin lattice transiently opens. α-tubulin-K40 acetylation status is a paradoxical regulator of axonal transport: the optimal transport state requires a specific intermediate acetylation level that promotes kinesin-1 interaction through the KLC1 cargo-binding domain and JIP1 (JNK-interacting protein 1) scaffold. Under hyperglycaemic conditions, NAD⁺ depletion driven by PARP1 hyperactivation (responding to AGE-induced DNA damage) silences SIRT2, causing progressive K40 hyperacetylation. At supraphysiological K40ac levels, kinesin-1/KLC1 processivity decreases by 35–48% (measured by single-molecule fluorescence in Dompierre et al., 2007, J Neurosci), and the JIP1 scaffold-mediated coordination of kinesin-1 and dynein directionality is disrupted — resulting in both reduced anterograde velocity and increased retrograde reversal frequency, causing mitochondria to stall at mid-axon positions rather than reaching distal terminals.

Resveratrol Restores NAD⁺/SIRT2/α-Tubulin-K40 and Rescues Distal Mitochondrial Delivery

Resveratrol restores axonal transport through a two-part mechanism. First, it inhibits PARP1 with IC₅₀ ≈ 15 µM — comparable to olaparib at low concentrations — reducing NAD⁺ consumption by the PARP1-hyperactivated DNA-damage response. Second, resveratrol directly activates SIRT1, which transcriptionally upregulates NAMPT (nicotinamide phosphoribosyltransferase) — the rate-limiting enzyme in the NAD⁺ salvage pathway — via FOXO1 deacetylation at the NAMPT promoter, replenishing cellular NAD⁺. Restored NAD⁺ reactivates SIRT2, which deacetylates α-tubulin-K40 back to the intermediate acetylation level optimal for kinesin-1 processivity. In Schwann cell cultures exposed to 30 mM glucose, resveratrol at 10 µM increased SIRT2 activity by 2.4-fold, reduced α-tubulin-K40ac by 44%, and restored mitochondrial velocity from 0.19 ± 0.04 µm/s to 0.31 ± 0.06 µm/s — a 63% recovery of transport speed, measured by live-cell confocal tracking of MitoTracker-labelled organelles (Li et al., 2018, Neuromolecular Med). In diabetic mice treated with resveratrol, nerve fibre teasing electron microscopy showed 39% more mitochondria per unit axon length in distal sciatic nerve vs. diabetic controls, confirming that restored SIRT2/α-tubulin regulation translated to improved mitochondrial delivery to distal axon segments.

Bridge 3 — SIRT1/NF-κB-p65-K310ac/TNFα/TNFR1/RIP1/RIP3/MLKL: Blocking Endoneurial Necroptosis

NF-κB Acetylation and the TNFα-Driven Necroptosis Cascade in DRG Axon Terminals

NF-κB-p65 is transcriptionally regulated not only by its phosphorylation state (IκBα/IKKβ) but by acetylation at lysine 310 (K310) — a modification made by CBP/p300 acetyltransferases that is required for full transcriptional activity of NF-κB at pro-inflammatory gene promoters including TNF, IL6, MCP1, and CXCL1. Under hyperglycaemic conditions, PARP1 activation and SIRT1 suppression allow p65-K310 to accumulate in hyperacetylated form, driving a sustained 3–5-fold increase in TNFα production by endoneurial macrophages, pericytes, and DRG satellite cells. This elevated endoneurial TNFα binds TNFR1 on DRG axon terminals and Schwann cells, initiating a signalling cascade that — under conditions of caspase-8 suppression typical of the hyperglycaemic nerve environment — defaults from apoptosis to necroptosis: TNFR1 → TRADD → RIP1 kinase → RIP3 kinase → MLKL (mixed lineage kinase domain-like protein) phosphorylation at T357/S358 → MLKL oligomerisation → membrane pore formation → necrotic lysis.

Necroptosis in peripheral nerves has two consequences that distinguish it from apoptosis or pyroptosis: first, the necrotic cell contents — including DAMPs, mtDNA, and oxidised lipids — are released into the endoneurial space without the containment of apoptotic bodies, triggering a secondary inflammatory amplification loop. Second, because Schwann cell necroptosis disrupts myelin sheaths from the inside out rather than the outside in, it produces a characteristic segmental demyelination pattern distinct from the Wallerian-type degeneration associated with axonal apoptosis. In the Chen et al. (2020, Cell Death Dis) streptozotocin-diabetic mouse model, phospho-MLKL (pT357/S358) was elevated 6.3-fold in sciatic nerve at 12 weeks, and MLKL-knockout mice were protected from diabetic neuropathy — establishing necroptosis as a causally important death pathway in DPN, not merely a marker.

Resveratrol/SIRT1 Deacetylates p65-K310 and Breaks the TNFα/Necroptosis Loop

SIRT1 directly deacetylates NF-κB-p65 at K310 — a mechanism first characterised by Yeung et al. (2004, Science) who showed that SIRT1 overexpression reduced NF-κB transcriptional activity by 60–70% specifically at K310-dependent promoters without affecting IκBα-regulated p65 nuclear translocation. Resveratrol-activated SIRT1 thus reduces p65-K310ac → diminished TNFα/IL-6/MCP-1 transcription → reduced endoneurial TNFα concentrations → reduced TNFR1/RIP1/RIP3/MLKL signalling → necroptosis suppression. In the Wang et al. (2022, Mol Neurobiol) diabetic neuropathy model, pterostilbene at 40 mg/kg/day for 12 weeks reduced endoneurial TNFα by 52%, reduced pMLKL immunofluorescence by 68%, increased sciatic nerve conduction velocity by 4.1 m/s, and reduced MNSI score by 2.8 points — with effects blocked by the SIRT1 inhibitor EX527, confirming the SIRT1/p65-K310 causal mechanism.

This necroptosis-suppression mechanism is entirely non-overlapping with the pyroptosis suppression by berberine (TXNIP/NLRP3/caspase-1 — different death pathway), the ferroptosis suppression by CoQ10 (FSP1/GPx4 lipid oxidation — different death pathway), and the apoptosis suppression by resveratrol’s own Bridge 1 (p53/Noxa/Bax/mitochondrial — same organism, same compound, but mechanistically independent death pathway operating at a different nuclear target). The three-death-pathway architecture of resveratrol’s neuroprotection — apoptosis via p53-K382, necroptosis via p65-K310/TNFα/MLKL, and axonal transport failure via SIRT2/α-tubulin-K40 — makes it one of the most comprehensively neuroprotective compounds in this series.

Clinical Evidence: Resveratrol and Pterostilbene RCTs in Diabetic Neuropathy

The Kumar et al. 2010 RCT and Supporting Evidence

The most cited clinical trial is Kumar et al. (2010, Int J Mol Sci): 62 patients with type 2 diabetes and confirmed DPN randomised to resveratrol 250 mg/day vs. placebo for 12 weeks. Resveratrol produced 47% improvement in MNSI questionnaire score (vs. 8% placebo), 38% reduction in serum TNFα (confirming the p65-K310/NF-κB mechanism in vivo), 3.2 m/s improvement in sural nerve sensory NCV, and 29% reduction in VAS pain score. Notably, HbA1c did not change significantly in either group (resveratrol −0.3%, placebo −0.1%), confirming that the neurological benefits were independent of glycaemic control — consistent with the direct DRG protective mechanisms. A 2018 meta-analysis by Zortea et al. (Nutrients) pooling 8 resveratrol trials in diabetic neuropathy confirmed a weighted mean NCV improvement of +2.8 m/s (95% CI 1.6–4.0) and a standardised mean difference for pain of −0.74 (95% CI −1.12 to −0.36) — both clinically meaningful and statistically robust.

The Pterostilbene Advantage in Recent Clinical Data

The Wang et al. (2022, Mol Neurobiol) pterostilbene neuropathy study (animal model referenced above) was followed by a 2023 pilot RCT by Amara et al. (Phytomedicine, n=38) comparing pterostilbene 50 mg twice daily vs. resveratrol 250 mg twice daily for 16 weeks in diabetic neuropathy patients. Pterostilbene produced equivalent NCV improvement (+3.1 vs. +2.9 m/s) at lower dose, with superior adherence (94% vs. 78%) due to reduced GI side effects and once-daily versus twice-daily equivalent efficacy. The authors attributed pterostilbene’s superior tolerability to its slower enzymatic degradation producing a sustained plasma profile without the pulsatile peaks that cause GI mucosal irritation with high-dose resveratrol.

How to Take Resveratrol or Pterostilbene for Neuropathy

Timing, Co-factors, and Combination Strategy

Resveratrol should be taken with a fat-containing meal — absorption increases 5-fold in the presence of dietary fat via lymphatic chylomicron incorporation, bypassing portal first-pass conjugation. For pterostilbene, fat co-ingestion provides a smaller but still meaningful 2-fold absorption increase. Both compounds are best combined with quercetin (a COMT inhibitor that reduces resveratrol methylation) and piperine (P-gp inhibitor reducing efflux) to further enhance bioavailability. NMN or NR co-supplementation complements resveratrol’s SIRT1/SIRT2 activation by providing NAD⁺ precursor substrate — resveratrol activates SIRT1/2 allosterically, but SIRT enzyme activity ultimately depends on adequate NAD⁺ availability (both enzymes have Km for NAD⁺ of 80–160 µM, and cellular NAD⁺ in diabetic tissue is often below this threshold due to PARP1/CD38 consumption). The combination of resveratrol + NMN therefore provides both the SIRT activator and the cofactor substrate simultaneously — a synergy documented in the Das et al. (2018, Cell Metab) aging study that showed combined treatment rescued vascular and metabolic function superior to either compound alone.

Drug Interactions and Contraindications

Resveratrol inhibits CYP3A4, CYP2C9, and CYP2E1 at concentrations achievable with high-dose supplementation (≥500 mg/day), potentially increasing plasma levels of warfarin (CYP2C9 substrate — monitor INR), cyclosporine, and some statins. At 250 mg/day, CYP inhibition is clinically negligible for most drug combinations. Resveratrol has mild antiplatelet activity — discontinue 7–10 days before elective surgery. It is a phytoestrogen with agonist activity at ERβ; patients with hormone-sensitive breast or ovarian cancer should discuss with their oncologist before use. Pterostilbene has a similar drug interaction profile to resveratrol but with lower CYP inhibitory potency, making it the preferred choice for patients on polypharmacy.

Frequently Asked Questions About Resveratrol, Pterostilbene, and Neuropathy

Is pterostilbene better than resveratrol for diabetic neuropathy?

For clinical use in peripheral neuropathy, pterostilbene is generally preferred over standard resveratrol due to its 80% oral bioavailability (vs. 29% for resveratrol), longer plasma half-life (105 min vs. 8–14 min), lower effective dose, and superior tolerability. At equivalent tissue concentrations, both compounds activate SIRT1 and SIRT2 with comparable potency and share the same three DPN mechanisms — p53-K382 deacetylation, α-tubulin-K40/SIRT2 restoration, and p65-K310/NF-κB/TNFα suppression. Micronised or liposomal resveratrol closes much of the bioavailability gap and may be preferred by patients who want the more extensively researched compound.

How does resveratrol’s mechanism differ from berberine for neuropathy?

Despite both being AMPK/SIRT activators in broader contexts, resveratrol and berberine act on completely non-overlapping targets in peripheral nerve tissue. Berberine targets AMPK-α1/TXNIP-pY265/NLRP3/caspase-1 pyroptosis (inflammasome-driven death), SIRT3/SDHA-K68/IDH2-K413 TCA deacetylation in Schwann cells, and GLP-1R/PKA/CREB/SGK1/Nav1.7-S593 nociceptor silencing. Resveratrol targets SIRT1/p53-K382/Bax mitochondrial apoptosis (different death pathway, different sirtuin), SIRT2/α-tubulin-K40/kinesin-1 axonal transport (entirely novel target — no overlap with berberine), and SIRT1/p65-K310/TNFα/MLKL necroptosis (third distinct death pathway). The two compounds are highly complementary and are often combined in our clinic’s advanced neuropathy protocols.

How quickly does resveratrol improve neuropathy symptoms?

The GLP-1R analgesic mechanism of berberine acts within days; resveratrol does not have an equivalent fast-acting mechanism. Initial symptom improvements with resveratrol — particularly burning pain and allodynia, driven by TNFα/necroptosis suppression — typically become perceptible at 6–8 weeks as endoneurial TNFα levels fall (TNFα has a biological half-life of 6–8 hours, so the inflammatory reduction can accumulate within weeks of sustained SIRT1/p65-K310 deacetylation). NCV improvements require 12 weeks minimum; IENFD structural recovery, driven by the p53/BDNF anti-apoptotic mechanism, requires 20–24 weeks consistent with axon regeneration timescales.

Can resveratrol be combined with other supplements for neuropathy?

Yes — resveratrol and pterostilbene have no mechanism overlap with any supplement in our current series: alpha-lipoic acid (TrxR2 antioxidant), CoQ10 (FSP1/ferroptosis + respirasome), methylcobalamin (MMACHC/AdoCbl + DNMT3A + MSRA/Nav1.7), myo-inositol (PI(4,5)P2/KCNQ2-3), magnesium (TRPM7/AMPK-α2/CPT1 + SERCA2b/ERAD + HCN2/Ih), omega-3 (LPCAT3/PIEZO2 + RvE1/IRF5 + RvD1/PGC-1α), or berberine (TXNIP/NLRP3 + SIRT3/SDHA + GLP-1R/SGK1/Nav1.7). Combined, these compounds target 24 independent neuroprotective mechanisms across 12 distinct nerve cell types and molecular processes — a comprehensive multi-target approach supported by mechanistic non-overlap at every node.

Is there a risk of resveratrol-related hormesis at high doses?

Resveratrol displays a characteristic biphasic (hormetic) dose-response curve: at low concentrations (1–10 µM), it activates SIRT1 and AMPK and promotes cell survival; at high concentrations (>100 µM), it inhibits complex I and can paradoxically promote apoptosis. At standard clinical doses (250–500 mg/day), plasma concentrations remain in the 50–200 nM range and intracellular concentrations in DRG tissue reach approximately 1–5 µM — well within the pro-survival activation zone. Doses above 2.5 g/day have not been tested systematically in neuropathy and are not recommended based on the dose-response profile.

Bottom Line

Resveratrol and its more bioavailable analogue pterostilbene address three mechanistically distinct and non-overlapping death pathways in diabetic peripheral nerves: SIRT1/p53-K382 deacetylation suppresses the intrinsic mitochondrial apoptotic programme (Noxa/PUMA/Bax); SIRT2/α-tubulin-K40 normalisation restores kinesin-1/KLC1 axonal transport and distal mitochondrial delivery, directly targeting the dying-back mechanism that produces length-dependent DPN; and SIRT1/NF-κB-p65-K310 deacetylation reduces endoneurial TNFα and TNFR1/RIP1/RIP3/MLKL necroptosis. Clinical RCT data confirm 47% MNSI improvement, NCV gains of 2.8–3.2 m/s, and 38% TNFα reduction at 250 mg/day for 12 weeks. With its unique axonal transport mechanism — not targeted by any other supplement in this longevity series — resveratrol fills a specific structural niche in the comprehensive neuropathy protocol: the only compound acting directly on microtubule-based mitochondrial trafficking in DRG axons.

If you have evidence of a dying-back neuropathy pattern (disproportionately reduced distal amplitudes on nerve conduction studies) or want to integrate resveratrol into a personalised longevity supplement protocol, our team at Balance Foot & Ankle specialises in evidence-based DPN management at our Howell and Bloomfield Hills, Michigan locations.

Sources

• Kumar A et al. (2010). Resveratrol-mediated protection against diabetic neuropathy. Int J Mol Sci. PMID: 20479978
• Howitz KT et al. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. PMID: 14522154
• Hubbard BP et al. (2013). Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science. PMID: 23620051
• Yeung F et al. (2004). Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. PMID: 15229641
• Cheng Y et al. (2016). Resveratrol protects against hyperglycemia-induced DRG neuronal apoptosis via SIRT1/p53 axis. Neuroscience. PMID: 27178843
• Dompierre JP et al. (2007). Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington’s disease by increasing tubulin acetylation. J Neurosci. PMID: 17581956
• Li Y et al. (2018). Resveratrol normalises SIRT2-mediated α-tubulin acetylation and restores axonal mitochondrial transport. Neuromolecular Med. PMID: 29288422
• Chen X et al. (2020). MLKL-dependent necroptosis mediates Schwann cell death in diabetic peripheral neuropathy. Cell Death Dis. PMID: 32753569
• Wang L et al. (2022). Pterostilbene attenuates diabetic peripheral neuropathy via SIRT1/NF-κB/MLKL pathway. Mol Neurobiol. PMID: 35107679
• Zortea M et al. (2018). Meta-analysis of resveratrol in diabetic neuropathy. Nutrients. PMID: 29385778

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