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, Akt, and ERK1/2, which suppress intrinsic and extrinsic apoptotic cascades. Humanin also reduces oxidative stress by preserving mitochondrial membrane potential and inhibiting cytochrome c release, while enhancing insulin sensitivity via modulation of insulin receptor substrate-1 (IRS-1) phosphorylation and AMPK activation. **Key Research Findings** Preclinical studies demonstrate Humanin’s neuroprotective efficacy in models of Alzheimer’s disease (AD), where it reduces amyloid-β (Aβ) toxicity and tau hyperphosphorylation. In cellular and rodent models of aging, Humanin improves mitochondrial function, extends lifespan, and attenuates age-related cognitive decline. The analog HNG (Humanin with a Ser14-to-Gly14 substitution) exhibits enhanced potency and stability. Humanin also shows cardioprotective effects in ischemia-reperfusion injury models and mitigates metabolic dysfunction by improving glucose uptake and reducing hepatic steatosis in diabetic rodents. **Clinical Relevance** Despite robust preclinical evidence, Humanin has not advanced to human clinical trials. Its short half-life, limited blood-brain barrier penetration, and need for parenteral administration pose translational challenges. 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 sarcopenia. For research purposes only — not medical advice.
Key data
C119H204N34O32S2Research & studies
Myeloid cells coordinately induce glioma cell-intrinsic (DDR) and cell-extrinsic (BTB) chemoresistance pathways via GP130 signaling.; Nanomolar humanin promotes TMZ resistance through DDR activation in humanized GBM models.; GP130 blockade attenuates both DDR activity and BTB formation, improving preclinical chemotherapy outcomes.; A translatable strategy with predictive markers is outlined to overcome TMZ resistance in GBMs.
NDEV levels of proBDNF, BDNF, and humanin increased in the exercise group but not in controls.; The increase in neuroprotective factors was especially pronounced in APOE4 carriers.; Inter-correlations between NDEV biomarkers at baseline were maintained after exercise.; Putative exerkine levels in NDEVs remained unchanged, suggesting different exercise pathways in neurons versus peripheral tissues.
Mitokines like FGF21, GDF15, and humanin mediate inter-tissue communication of mitochondrial stress.; Altered mitokine levels are associated with aging and age-related metabolic, cardiovascular, and neurological diseases.; Both reduced and excessive mitokine concentrations can have deleterious consequences, including cancer and heart failure.; Regular exercise maintains mitokine homeostasis and is associated with increased lifespan.
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 523 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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