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Study · Animal study (in vivo) · mouse · 2012

9 results

Exendin-4 ameliorates motor neuron degeneration in cellular and animal models of amyotrophic lateral sclerosis.

Li Y, Chigurupati S, Holloway HW, Mughal M, Tweedie D, Bruestle DA, Mattson MP, Wang Y, Harvey BK, Ray B, Lahiri DK, Greig NH

PloS one23 Feb 2012Cited by 114 (Europe PMC)

PMID22384126 (opens in a new tab)PMCIDPMC3285661 (opens in a new tab)DOI10.1371/journal.pone.0032008 (opens in a new tab)PepBankPUB-22384126
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Summary

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by a progressive loss of lower motor neurons in the spinal cord. The incretin hormone, glucagon-like peptide-1 (GLP-1), facilitates insulin signaling, and the long acting GLP-1 receptor agonist exendin-4 (Ex-4) is currently used as an anti-diabetic drug. GLP-1 receptors are widely expressed in the brain and spinal cord, and our prior studies have shown that Ex-4 is neuroprotective in several neurodegenerative disease rodent models, including stroke, Parkinson's disease and Alzheimer's disease. Here we hypothesized that Ex-4 may provide neuroprotective activity in ALS, and hence characterized Ex-4 actions in both cell culture (NSC-19 neuroblastoma cells) and in vivo (SOD1 G93A mutant mice) models of ALS. Ex-4 proved to be neurotrophic in NSC-19 cells, elevating choline acetyltransferase (ChAT) activity, as well as neuroprotective, protecting cells from hydrogen peroxide-induced oxidative stress and staurosporine-induced apoptosis. Additionally, in both wild-type SOD1 and mutant SOD1 (G37R) stably transfected NSC-19 cell lines, Ex-4 protected against trophic factor withdrawal-induced toxicity. To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion. ALS mice treated with Ex-4 showed improved glucose tolerance and normalization of behavior, as assessed by running wheel, compared to control ALS mice. Furthermore, Ex-4 treatment attenuated neuronal cell death in the lumbar spinal cord; immunohistochemical analysis demonstrated the rescue of neuronal markers, such as ChAT, associated with motor neurons. Together, our results suggest that GLP-1 receptor agonists warrant further evaluation to assess whether their neuroprotective potential is of therapeutic relevance in ALS.
CC0Text from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In ALS mice, exendin‑4 improved glucose tolerance compared with control ALS mice.

    In plain wordsIn mice with ALS, exendin‑4 improved glucose tolerance compared with control mice.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseGlucose tolerance
    Study

    mousen: not reported in source

    SOD1 mutant ALS mice
    Comparator
    Control ALS mice
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated · subcutaneous osmotic pump · From 6 weeks of age to end-stage diseaseAs given in this study (mouse).

    Source sentences

    Summary
    ALS mice treated with Ex-4 showed improved glucose tolerance and normalization of behavior, as assessed by running wheel, compared to control ALS mice.
    1 context sentence
    Summary · context
    To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In ALS mice, exendin‑4 normalized running wheel behavior compared with control ALS mice.

    In plain wordsIn mice with ALS, exendin‑4 normalized wheel-running behavior compared with control mice.

    Peptide
    Exenatide (exendin-4)
    Outcome
    Not applicableRunning wheel behavior
    Study

    mousen: not reported in source

    SOD1 mutant ALS mice
    Comparator
    Control ALS mice
    Outcome group
    Exercise and physical function · Nervous system and cognition
    Studied dose
    Dose not stated · subcutaneous osmotic pump · From 6 weeks of age to end-stage diseaseAs given in this study (mouse).

    Source sentences

    Summary
    ALS mice treated with Ex-4 showed improved glucose tolerance and normalization of behavior, as assessed by running wheel, compared to control ALS mice.
    1 context sentence
    Summary · context
    To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In ALS mice, exendin‑4 attenuated neuronal cell death in the lumbar spinal cord.

    In plain wordsIn mice with ALS, exendin‑4 reduced nerve cell death in the lower spinal cord.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseLumbar spinal neuronal death
    Study

    mousen: not reported in source

    SOD1 mutant ALS mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · subcutaneous osmotic pump · From 6 weeks of age to end-stage diseaseAs given in this study (mouse).

    Source sentences

    Summary
    Furthermore, Ex-4 treatment attenuated neuronal cell death in the lumbar spinal cord; immunohistochemical analysis demonstrated the rescue of neuronal markers, such as ChAT, associated with motor neurons.
    1 context sentence
    Summary · context
    To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion.
  4. 04AnimalAnimal study (in vivo)Activity measurement

    In ALS mice, exendin‑4 rescued neuronal markers associated with motor neurons, including ChAT.

    In plain wordsIn mice with ALS, exendin‑4 restored markers associated with motor nerve cells.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseMotor neuron markers
    Study

    mousen: not reported in source

    SOD1 mutant ALS mice
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · subcutaneous osmotic pump · From 6 weeks of age to end-stage diseaseAs given in this study (mouse).

    Source sentences

    Summary
    Furthermore, Ex-4 treatment attenuated neuronal cell death in the lumbar spinal cord; immunohistochemical analysis demonstrated the rescue of neuronal markers, such as ChAT, associated with motor neurons.
    1 context sentence
    Summary · context
    To assess in vivo translation, SOD1 mutant mice were administered vehicle or Ex-4 at 6-weeks of age onwards to end-stage disease via subcutaneous osmotic pump to provide steady-state infusion.
  5. 05LabIn vitro (cells)Activity measurement

    In NSC-19 cells, exendin‑4 increased choline acetyltransferase activity.

    In plain wordsIn cells, exendin‑4 increased an enzyme linked to nerve cell function.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseCholine acetyltransferase activity
    Study

    n: not reported in source

    NSC-19 neuroblastoma cells
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Ex-4 proved to be neurotrophic in NSC-19 cells, elevating choline acetyltransferase (ChAT) activity, as well as neuroprotective, protecting cells from hydrogen peroxide-induced oxidative stress and staurosporine-induced apoptosis.
  6. 06LabIn vitro (cells)Efficacy outcome

    In NSC-19 cells, exendin‑4 protected against hydrogen peroxide-induced oxidative stress.

    In plain wordsIn cells, exendin‑4 protected against oxidative stress from hydrogen peroxide.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseOxidative stress injury
    Study

    n: not reported in source

    NSC-19 neuroblastoma cells
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Ex-4 proved to be neurotrophic in NSC-19 cells, elevating choline acetyltransferase (ChAT) activity, as well as neuroprotective, protecting cells from hydrogen peroxide-induced oxidative stress and staurosporine-induced apoptosis.
  7. 07LabIn vitro (cells)Efficacy outcome

    In NSC-19 cells, exendin‑4 protected against staurosporine-induced apoptosis.

    In plain wordsIn cells, exendin‑4 protected against cell death induced by staurosporine.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseApoptosis
    Study

    n: not reported in source

    NSC-19 neuroblastoma cells
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Ex-4 proved to be neurotrophic in NSC-19 cells, elevating choline acetyltransferase (ChAT) activity, as well as neuroprotective, protecting cells from hydrogen peroxide-induced oxidative stress and staurosporine-induced apoptosis.
  8. 08LabIn vitro (cells)Efficacy outcome

    In wild-type SOD1-transfected NSC-19 cells, exendin‑4 protected against trophic factor withdrawal toxicity.

    In plain wordsIn cells with wild-type SOD1, exendin‑4 protected against toxicity after growth factor withdrawal.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseTrophic factor withdrawal toxicity
    Study

    n: not reported in source

    Wild-type SOD1-transfected NSC-19 cells
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Additionally, in both wild-type SOD1 and mutant SOD1 (G37R) stably transfected NSC-19 cell lines, Ex-4 protected against trophic factor withdrawal-induced toxicity.
  9. 09LabIn vitro (cells)Efficacy outcome

    In mutant SOD1-transfected NSC-19 cells, exendin‑4 protected against trophic factor withdrawal toxicity.

    In plain wordsIn cells with mutant SOD1, exendin‑4 protected against toxicity after growth factor withdrawal.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseTrophic factor withdrawal toxicity
    Study

    n: not reported in source

    Mutant SOD1 G37R-transfected NSC-19 cells
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Additionally, in both wild-type SOD1 and mutant SOD1 (G37R) stably transfected NSC-19 cell lines, Ex-4 protected against trophic factor withdrawal-induced toxicity.

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 2Current

    22 Oct 2026, 02:26 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

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