Humanin
preclinicalAlso known as: HN, HNG analog
**Mechanism of Action** Humanin (HN) is a 24-amino acid mitochondrial-derived peptide that exerts cytoprotective effects primarily through binding to a heterotrimeric receptor complex comprising ciliary neurotrophic factor receptor α (CNTFR), gp130, and WSX-1. This interaction activates downstream signaling pathways, including STAT3 and PI3K/Akt, which suppress apoptosis by inhibiting Bax translocation and cytochrome c release. Additionally, Humanin enhances insulin sensitivity by reducing endoplasmic reticulum stress and modulating JNK activity, while also attenuating oxidative stress via upregulation of antioxidant enzymes. **Key Research Findings** Preclinical studies demonstrate that Humanin protects against neuronal cell death in models of Alzheimer’s disease (AD) by reducing amyloid-β toxicity and tau hyperphosphorylation. In cardiovascular models, it mitigates ischemia-reperfusion injury and improves mitochondrial function. The analog HNG (Humanin with a glycine substitution at position 14) shows enhanced potency and stability. Humanin also improves metabolic parameters in diabetic rodent models, including reduced fasting glucose and improved glucose tolerance, through mechanisms involving AMPK activation and suppression of hepatic gluconeogenesis. **Clinical Relevance** Despite robust preclinical evidence for neuroprotection, metabolic regulation, and anti-aging effects, Humanin has not advanced to human clinical trials. Its short half-life and limited bioavailability remain key translational barriers. Current research focuses on developing stable analogs and delivery systems to harness its therapeutic potential for age-related diseases, including AD, type 2 diabetes, and cardiovascular disorders. For research purposes only — not medical advice.
Key data
C119H204N34O32S2Research & studies
Human efferocytic macrophages show common modulation of mitochondrial metabolism-related genes, including PLIN5 and MTLN.; HUMANIN (MT-RNR2) is produced early during resolution of inflammation in a mouse peritonitis model.; Preventive HUMANIN administration reduces leukocyte infiltration and pro-inflammatory cytokines in mice.; HUMANIN dampens pro-inflammatory cytokine secretion in primary human neutrophils and is detected in human periodontitis gingival fluid.
MDPs regulate apoptosis, inflammation, and oxidative stress, key processes in cardiovascular disease.; MDP levels decrease with aging and in the presence of CVDs, indicating potential as diagnostic biomarkers.; MDPs may offer a novel therapeutic strategy for treating cardiovascular diseases.; The review covers MDP biogenesis, types, and mechanisms linking them to CVD onset and progression.
Myeloid cells and GBM interaction activates GP130 signaling to induce chemoresistance.; Humanin peptide promotes TMZ resistance via DDR activation at nanomolar concentrations.; GP130 blockade reduces both DDR activity and BTB formation, enhancing chemotherapy.; A translatable strategy with predictive markers for improving GBM chemotherapy is outlined.
Frequently asked questions
What is Humanin?
**Mechanism of Action** Humanin (HN) is a 24-amino acid mitochondrial-derived peptide that exerts cytoprotective effects primarily through binding to a heterotrimeric receptor complex comprising ciliary neurotrophic factor receptor α (CNTFR), gp130, and WSX-1. This interaction activates downstream signaling pathways, i
How does Humanin work?
Mitochondrial-derived 24-aa peptide with cytoprotective, anti-apoptotic, and insulin-sensitizing effects in aging and neurodegeneration models.
What is the research status of Humanin?
Humanin is currently classified as preclinical, with 534 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Humanin?
Humanin has a molecular weight of approximately 2687.2 g/mol (formula C119H204N34O32S2).
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