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Study · Animal study (in vivo) · mouse · 2026

8 results

Thymosin Alpha-1 Provides Direct Neuroprotection by Engaging the Orexin Receptor HCRTR1 to Suppress Neuronal Necroptosis.

Kang X, Wang S, Zhang L, Hu M, Su X, Liu Y, Qin Q, Yi H, Yuan L, Cai W, Wei L, Lu Z

Advanced science (Weinheim, Baden-Wurttemberg, Germany)3 Sept 2026

PMID42693587 (opens in a new tab)PMCIDPMC13542392 (opens in a new tab)DOI10.1002/advs.202522372 (opens in a new tab)PepBankPUB-42693587
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Summary

Communication between the immune system and the brain is critical for neuronal health, yet the molecular signals that mediate this crosstalk are not fully understood. Here, we uncover an unexpected and direct neuroprotective axis linking the thymus to the central nervous system (CNS). We show that the thymus-derived peptide Thymosin alpha-1 (Tα1) functions as a non-canonical ligand for the Hypocretin (Orexin) Receptor 1 (HCRTR1), a classical neuropeptide receptor on neurons. This engagement shields neurons from cell death by suppressing the activity of Receptor-Interacting Protein Kinase 3 (RIPK3), a central executioner of necroptosis. The physiological relevance of this pathway is highlighted in ischemic stroke, where we found that circulating Tα1 levels were significantly reduced in patients and mice, strongly correlating with disease severity. Genetic deletion of the Tα1-encoding gene Ptma exacerbated stroke injury, whereas therapeutic administration of Tα1 conferred robust neuroprotection and improved functional recovery. Our findings identify a novel thymus-brain signaling pathway, revealing a new neuroprotective function for an immune peptide and an unexpected role for a canonical neuronal receptor. This work establishes Tα1 as a promising dual-action therapeutic candidate, capable of both direct neuronal protection and systemic immunomodulation.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

4 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice with stroke, therapeutic administration of thymosin alpha‑1 conferred robust neuroprotection.

    In plain wordsIn mice with stroke, giving thymosin alpha‑1 protected the brain.

    Peptide
    Thymosin alpha-1
    Outcome
    IncreaseNeuroprotection after therapeutic Tα1
    Study

    mousen: not reported in source

    Mouse stroke model
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    whereas therapeutic administration of Tα1 conferred robust neuroprotection and improved functional recovery.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice with stroke, therapeutic administration of thymosin alpha‑1 improved functional recovery.

    In plain wordsIn mice with stroke, giving thymosin alpha‑1 improved recovery of function.

    Peptide
    Thymosin alpha-1
    Outcome
    IncreaseFunctional recovery after therapeutic Tα1
    Study

    mousen: not reported in source

    Mouse stroke model
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    whereas therapeutic administration of Tα1 conferred robust neuroprotection and improved functional recovery.
  3. 03LabIn vitro (cells)Mechanism

    Thymosin alpha‑1 functions as a non-canonical ligand for the Hypocretin (Orexin) Receptor 1 (HCRTR1) on neurons.

    In plain wordsIn lab tests, thymosin alpha‑1 acted as a ligand for the orexin receptor 1 on neurons.

    Peptide
    Thymosin alpha-1
    Outcome
    Not applicableHCRTR1 ligand activity
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We show that the thymus-derived peptide Thymosin alpha-1 (Tα1) functions as a non-canonical ligand for the Hypocretin (Orexin) Receptor 1 (HCRTR1), a classical neuropeptide receptor on neurons.
  4. 04LabIn vitro (cells)Mechanism

    Engagement of HCRTR1 by thymosin alpha‑1 shielded neurons from cell death by suppressing RIPK3 activity.

    In plain wordsIn lab tests, thymosin alpha‑1 protected neurons from cell death by lowering RIPK3 activity.

    Peptide
    Thymosin alpha-1
    Outcome
    DecreaseNeuronal cell death and RIPK3 activity
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    This engagement shields neurons from cell death by suppressing the activity of Receptor-Interacting Protein Kinase 3 (RIPK3), a central executioner of necroptosis.

Natural levels measured4

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

  1. 05HumanEndogenous levelObservational studyOther

    Circulating levels of the body's own thymosin alpha‑1 were significantly reduced in patients with ischemic stroke.

    In plain wordsPeople with ischemic stroke had lower levels of the body's own thymosin alpha‑1 in blood.

    Peptide
    Thymosin alpha-1
    Outcome
    DecreaseCirculating Tα1 in ischemic stroke patients
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition

    Source sentences

    Summary
    circulating Tα1 levels were significantly reduced in patients and mice, strongly correlating with disease severity.

    This result measures the body's own Thymosin alpha-1. Nobody was given the peptide. It is not evidence about taking it.

  2. 06HumanEndogenous levelObservational studyOther

    Lower circulating levels of the body's own thymosin alpha‑1 correlated strongly with disease severity in ischemic stroke.

    In plain wordsIn ischemic stroke, lower levels of the body's own thymosin alpha‑1 were linked to more severe disease.

    Peptide
    Thymosin alpha-1
    Outcome
    Not applicableCorrelation of circulating Tα1 with stroke severity
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition

    Source sentences

    Summary
    strongly correlating with disease severity.

    This result measures the body's own Thymosin alpha-1. Nobody was given the peptide. It is not evidence about taking it.

  3. 07AnimalEndogenous levelAnimal study (in vivo)Other

    Circulating levels of the body's own thymosin alpha‑1 were significantly reduced in mice with ischemic stroke.

    In plain wordsIn mice with ischemic stroke, the body's own thymosin alpha‑1 levels in blood were lower.

    Peptide
    Thymosin alpha-1
    Outcome
    DecreaseCirculating Tα1 in stroke mice
    Study

    mousen: not reported in source

    Mouse ischemic stroke
    Outcome group
    Neuroprotection · Nervous system and cognition

    Source sentences

    Summary
    circulating Tα1 levels were significantly reduced in patients and mice, strongly correlating with disease severity.

    This result measures the body's own Thymosin alpha-1. Nobody was given the peptide. It is not evidence about taking it.

  4. 08AnimalEndogenous levelAnimal study (in vivo)Mechanism

    In mice, genetic deletion of the Tα1-encoding gene Ptma exacerbated stroke injury.

    In plain wordsIn mice, removing the gene for the body's own thymosin alpha‑1 made stroke injury worse.

    Peptide
    Thymosin alpha-1
    Outcome
    IncreaseStroke injury after Ptma deletion
    Study

    mousen: not reported in source

    Ptma gene deletion in mouse stroke
    Outcome group
    Neuroprotection · Nervous system and cognition

    Source sentences

    Summary
    Genetic deletion of the Tα1-encoding gene Ptma exacerbated stroke injury

    This result measures the body's own Thymosin alpha-1. Nobody was given the peptide. It is not evidence about taking it.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 3Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 2

    9 Oct 2026, 03:03 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:02 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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