PPARγ agonists: potential treatment for autism spectrum disorder by inhibiting the canonical WNT/β-catenin pathway

doi:10.1038/s41380-018-0131-4

Review

. 2019 May;24(5):643-652.

doi: 10.1038/s41380-018-0131-4. Epub 2018 Aug 13.

PPARγ agonists: potential treatment for autism spectrum disorder by inhibiting the canonical WNT/β-catenin pathway

Alexandre Vallée^{1

2}, Jean-Noël Vallée^{3

4}, Yves Lecarpentier⁵

Affiliations

¹ Paris-Descartes University; Diagnosis and Therapeutic Center, Hôtel-Dieu Hospital; AP-HP, Paris, France. alexandre.g.vallee@gmail.com.
² Laboratoire de Mathématiques et Applications (LMA), UMR CNRS 7348, Université de Poitiers, Poitiers, France. alexandre.g.vallee@gmail.com.
³ Centre Hospitalier Universitaire (CHU) Amiens Picardie, Université Picardie Jules Verne (UPJV), 80054, Amiens, France.
⁴ Laboratoire de Mathématiques et Applications (LMA), UMR CNRS 7348, Université de Poitiers, Poitiers, France.
⁵ Centre de Recherche Clinique, Grand Hôpital de l'Est Francilien (GHEF), 6-8 rue Saint-fiacre, 77100, Meaux, France.

PMID: 30104725
DOI: 10.1038/s41380-018-0131-4

Review

PPARγ agonists: potential treatment for autism spectrum disorder by inhibiting the canonical WNT/β-catenin pathway

Alexandre Vallée et al. Mol Psychiatry. 2019 May.

. 2019 May;24(5):643-652.

doi: 10.1038/s41380-018-0131-4. Epub 2018 Aug 13.

Authors

Alexandre Vallée^{1

2}, Jean-Noël Vallée^{3

4}, Yves Lecarpentier⁵

Affiliations

¹ Paris-Descartes University; Diagnosis and Therapeutic Center, Hôtel-Dieu Hospital; AP-HP, Paris, France. alexandre.g.vallee@gmail.com.
² Laboratoire de Mathématiques et Applications (LMA), UMR CNRS 7348, Université de Poitiers, Poitiers, France. alexandre.g.vallee@gmail.com.
³ Centre Hospitalier Universitaire (CHU) Amiens Picardie, Université Picardie Jules Verne (UPJV), 80054, Amiens, France.
⁴ Laboratoire de Mathématiques et Applications (LMA), UMR CNRS 7348, Université de Poitiers, Poitiers, France.
⁵ Centre de Recherche Clinique, Grand Hôpital de l'Est Francilien (GHEF), 6-8 rue Saint-fiacre, 77100, Meaux, France.

PMID: 30104725
DOI: 10.1038/s41380-018-0131-4

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by a deficit in social interactions and communication with repetitive and restrictive behavior. No curative treatments are available for ASD. Pharmacological treatments do not address the core ASD behaviors, but target comorbid symptoms. Dysregulation of the core neurodevelopmental pathways is associated with the clinical presentation of ASD, and the canonical WNT/β-catenin pathway is one of the major pathways involved. The canonical WNT/β-catenin pathway participates in the development of the central nervous system, and its dysregulation involves developmental cognitive disorders. In numerous tissues, the canonical WNT/β-catenin pathway and peroxisome proliferator-activated receptor gamma (PPARγ) act in an opposed manner. In ASD, the canonical WNT/β-catenin pathway is increased while PPARγ seems to be decreased. PPARγ agonists present a beneficial effect in treatment for ASD children through their anti-inflammatory role. Moreover, they induce the inhibition of the canonical WNT/β-catenin pathway in several pathophysiological states. We focus this review on the hypothesis of an opposed interplay between PPARγ and the canonical WNT/β-catenin pathway in ASD and the potential role of PPARγ agonists as treatment for ASD.

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References

1. Posar A, Resca F, Visconti P. Autism according to diagnostic and statistical manual of mental disorders 5(th) edition: The need for further improvements. J Pediatr Neurosci. 2015;10:146–8. - PubMed - PMC
1. Ospina MB, Krebs Seida J, Clark B, Karkhaneh M, Hartling L, Tjosvold L, et al. Behavioural and developmental interventions for autism spectrum disorder: a clinical systematic review. PLoS One 2008;3:e3755. - PubMed - PMC
1. Altemeier WA,Altemeier LE, How can early, intensive training help a genetic disorder?. Pediatr Ann. 2009;38:167–70. - PubMed
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1. Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A. The familial risk of autism. JAMA 2014;311:1770–7. - PubMed - PMC

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[1] Posar A, Resca F, Visconti P. Autism according to diagnostic and statistical manual of mental disorders 5(th) edition: The need for further improvements. J Pediatr Neurosci. 2015;10:146–8. - PubMed - PMC

[2] Posar A, Resca F, Visconti P. Autism according to diagnostic and statistical manual of mental disorders 5(th) edition: The need for further improvements. J Pediatr Neurosci. 2015;10:146–8. - PubMed - PMC

[3] Ospina MB, Krebs Seida J, Clark B, Karkhaneh M, Hartling L, Tjosvold L, et al. Behavioural and developmental interventions for autism spectrum disorder: a clinical systematic review. PLoS One 2008;3:e3755. - PubMed - PMC

[4] Ospina MB, Krebs Seida J, Clark B, Karkhaneh M, Hartling L, Tjosvold L, et al. Behavioural and developmental interventions for autism spectrum disorder: a clinical systematic review. PLoS One 2008;3:e3755. - PubMed - PMC

[5] Altemeier WA,Altemeier LE, How can early, intensive training help a genetic disorder?. Pediatr Ann. 2009;38:167–70. - PubMed

[6] Altemeier WA,Altemeier LE, How can early, intensive training help a genetic disorder?. Pediatr Ann. 2009;38:167–70. - PubMed

[7] Doyle CA, McDougle CJ. Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan. Dialog- Clin Neurosci. 2012;14:263–79.

[8] Doyle CA, McDougle CJ. Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan. Dialog- Clin Neurosci. 2012;14:263–79.

[9] Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A. The familial risk of autism. JAMA 2014;311:1770–7. - PubMed - PMC

[10] Sandin S, Lichtenstein P, Kuja-Halkola R, Larsson H, Hultman CM, Reichenberg A. The familial risk of autism. JAMA 2014;311:1770–7. - PubMed - PMC

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PPARγ agonists: potential treatment for autism spectrum disorder by inhibiting the canonical WNT/β-catenin pathway

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PPARγ agonists: potential treatment for autism spectrum disorder by inhibiting the canonical WNT/β-catenin pathway

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