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Wnt Signaling: Role in Alzheimer Disease and Schizophrenia

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Abstract

Wnt signaling function starts during the development of the nervous system and is crucial for synaptic plasticity in the adult brain. Clearly Wnt effects in synaptic and plastic processes are relevant, however the implication of this pathway in the prevention of neurodegenerative diseases that produce synaptic impairment, is even more interesting. Several years ago our laboratory found a relationship between the loss of Wnt signaling and the neurotoxicity of the amyloid-β-peptide (Aβ), one of the main players in Alzheimer’s disease (AD). Moreover, the activation of the Wnt signaling cascade prevents Aβ-dependent cytotoxic effects. In fact, disrupted Wnt signaling may be a direct link between Aβ-toxicity and tau hyperphosphorylation, ultimately leading to impaired synaptic plasticity and/or neuronal degeneration, indicating that a single pathway can account for both neuro-pathological lesions and altered synaptic function. These observations, suggest that a sustained loss of Wnt signaling function may be a key relevant factor in the pathology of AD. On the other hand, Schizophrenia remains one of the most debilitating and intractable illness in psychiatry. Since Wnt signaling is important in organizing the developing brain, it is reasonable to propose that defects in Wnt signaling could contribute to Schizophrenia, particularly since the neuro-developmental hypothesis of the disease implies subtle dys-regulation of brain development, including some core components of the Wnt signaling pathways such as GSK-3β or Disrupted in Schizophrenia-1 (DISC-1). This review focuses on the relationship between Wnt signaling and its potential relevance for the treatment of neurodegenerative and neuropsychiatric diseases including AD and Schizophrenia.

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Acknowledgments

This work was supported by the Basal Center of Excellence in Science and Technology - CONICYT CARE PFB12/2007, Fondecyt Nº 1120156 to NCI and grants from Fondecyt N° 11090059 and CID-01/2006 from Universidad de Valparaiso to MF. CM-O, was a Research Associate of the CARE Biomedical Center.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, 8331150, Santiago, Chile

    Nibaldo C. Inestrosa & Carla Montecinos-Oliva

  2. Centro de Neurobiología y Plasticidad Cerebral, Departamento de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile

    Marco Fuenzalida

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  1. Nibaldo C. Inestrosa
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  2. Carla Montecinos-Oliva
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  3. Marco Fuenzalida
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Correspondence to Nibaldo C. Inestrosa.

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Inestrosa, N.C., Montecinos-Oliva, C. & Fuenzalida, M. Wnt Signaling: Role in Alzheimer Disease and Schizophrenia. J Neuroimmune Pharmacol 7, 788–807 (2012). https://doi.org/10.1007/s11481-012-9417-5

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  • DOI: https://doi.org/10.1007/s11481-012-9417-5

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