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Study · Animal study (in vivo) · mouse · 2017

6 results

Chronic 5-Aminoimidazole-4-Carboxamide-1-β-d-Ribofuranoside Treatment Induces Phenotypic Changes in Skeletal Muscle, but Does Not Improve Disease Outcomes in the R6/2 Mouse Model of Huntington's Disease.

Paré MF, Jasmin BJ

Frontiers in neurology27 Sept 2017Cited by 4 (Europe PMC)

PMID29021780 (opens in a new tab)PMCIDPMC5623671 (opens in a new tab)DOI10.3389/fneur.2017.00516 (opens in a new tab)PepBankPUB-29021780
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Summary

Huntington's disease (HD) is an autosomal dominant neurodegenerative genetic disorder characterized by motor, cognitive, and psychiatric symptoms. It is well established that regular physical activity supports brain health, benefiting cognitive function, mental health as well as brain structure and plasticity. Exercise mimetics (EMs) are a group of drugs and small molecules that target signaling pathways in skeletal muscle known to be activated by endurance exercise. The EM 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) has been shown to induce cognitive benefits in healthy mice. Since AICAR does not readily cross the blood-brain barrier, its beneficial effect on the brain has been ascribed to its impact on skeletal muscle. Our objective, therefore, was to examine the effect of chronic AICAR treatment on the muscular and neurological pathology in a mouse model of HD. To this end, R6/2 mice were treated with AICAR for 8 weeks and underwent regular neurobehavioral testing. Under our conditions, AICAR increased expression of PGC-1α, a powerful phenotypic modifier of muscle, and induced the expected shift toward a more oxidative muscle phenotype in R6/2 mice. However, this treatment failed to induce benefits on HD progression. Indeed, neurobehavioral deficits, striatal, and muscle mutant huntingtin aggregate density, as well as muscle atrophy were not mitigated by the chronic administration of AICAR. Although the muscle adaptations seen in HD mice following AICAR treatment may still provide therapeutically relevant benefits to patients with limited mobility, our findings indicate that under our experimental conditions, AICAR had no effect on several hallmarks of HD.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

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

  1. 01AnimalAnimal study (in vivo)Mechanism

    In R6/2 mice, AICAR increased muscle PGC-1α expression.

    In plain wordsIn mice with Huntington's disease, AICAR increased muscle PGC-1α expression.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseMuscle PGC-1α expression
    Study

    mousen: not reported in source

    R6/2 Huntington's disease model
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Under our conditions, AICAR increased expression of PGC-1α, a powerful phenotypic modifier of muscle, and induced the expected shift toward a more oxidative muscle phenotype in R6/2 mice.
    1 context sentence
    Summary · context
    To this end, R6/2 mice were treated with AICAR for 8 weeks and underwent regular neurobehavioral testing.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In R6/2 mice, AICAR shifted muscle toward a more oxidative phenotype.

    In plain wordsIn mice with Huntington's disease, AICAR shifted muscle toward a more oxidative phenotype.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseOxidative muscle phenotype
    Study

    mousen: not reported in source

    R6/2 Huntington's disease model
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Under our conditions, AICAR increased expression of PGC-1α, a powerful phenotypic modifier of muscle, and induced the expected shift toward a more oxidative muscle phenotype in R6/2 mice.
    1 context sentence
    Summary · context
    To this end, R6/2 mice were treated with AICAR for 8 weeks and underwent regular neurobehavioral testing.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In R6/2 mice, AICAR did not mitigate neurobehavioral deficits.

    In plain wordsIn mice with Huntington's disease, AICAR did not reduce neurobehavioral deficits.

    Peptide
    AICAR (acadesine)
    Outcome
    No significant changeNeurobehavioral deficits
    Study

    mousen: not reported in source

    R6/2 Huntington's disease model
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Indeed, neurobehavioral deficits, striatal, and muscle mutant huntingtin aggregate density, as well as muscle atrophy were not mitigated by the chronic administration of AICAR.
    1 context sentence
    Summary · context
    To this end, R6/2 mice were treated with AICAR for 8 weeks and underwent regular neurobehavioral testing.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In R6/2 mice, AICAR did not mitigate striatal mutant huntingtin aggregate density.

    In plain wordsIn mice with Huntington's disease, AICAR did not reduce mutant huntingtin aggregates in the striatum.

    Peptide
    AICAR (acadesine)
    Outcome
    No significant changeStriatal mutant huntingtin aggregate density
    Study

    mousen: not reported in source

    R6/2 Huntington's disease model
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Indeed, neurobehavioral deficits, striatal, and muscle mutant huntingtin aggregate density, as well as muscle atrophy were not mitigated by the chronic administration of AICAR.
    1 context sentence
    Summary · context
    To this end, R6/2 mice were treated with AICAR for 8 weeks and underwent regular neurobehavioral testing.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In R6/2 mice, AICAR did not mitigate muscle mutant huntingtin aggregate density.

    In plain wordsIn mice with Huntington's disease, AICAR did not reduce mutant huntingtin aggregates in muscle.

    Peptide
    AICAR (acadesine)
    Outcome
    No significant changeMuscle mutant huntingtin aggregate density
    Study

    mousen: not reported in source

    R6/2 Huntington's disease model
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Indeed, neurobehavioral deficits, striatal, and muscle mutant huntingtin aggregate density, as well as muscle atrophy were not mitigated by the chronic administration of AICAR.
    1 context sentence
    Summary · context
    To this end, R6/2 mice were treated with AICAR for 8 weeks and underwent regular neurobehavioral testing.
  6. 06AnimalAnimal study (in vivo)Efficacy outcome

    In R6/2 mice, AICAR did not mitigate muscle atrophy.

    In plain wordsIn mice with Huntington's disease, AICAR did not reduce muscle wasting.

    Peptide
    AICAR (acadesine)
    Outcome
    No significant changeMuscle atrophy
    Study

    mousen: not reported in source

    R6/2 Huntington's disease model
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Indeed, neurobehavioral deficits, striatal, and muscle mutant huntingtin aggregate density, as well as muscle atrophy were not mitigated by the chronic administration of AICAR.
    1 context sentence
    Summary · context
    To this end, R6/2 mice were treated with AICAR for 8 weeks and underwent regular neurobehavioral testing.

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

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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