Authors: Li, F.; Chong, Z. Z.; Maiese, K.

Source: Current Neurovascular Research, Volume 2, Number 4, October 2005 , pp. 331-340(10)

Publisher: Bentham Science Publishers

Abstract:

Wnt proteins are cysteine-rich glycosylated proteins named after the Drosophilia Wingless (Wg) and the mouse Int-1 genes that play a role in embryonic cell patterning, proliferation, differentiation, orientation, adhesion, survival, and programmed cell death (PCD). Wnt proteins involve at least two intracellular signaling pathways. One pathway controls target gene transcription through -catenin, generally referred to as the canonical pathway and a second pathway pertains to intracellular calcium (Ca2+) release which is termed the non-canonical or Wnt/ Ca2+ pathway. The majority of Wnt proteins activate gene transcription through the canonical signaling pathway regulated by pathways that include the Frizzled transmembrane receptor and the co-receptor LRP-5/6, Dishevelled, glycogen synthase kinase-3 (GSK-3), adenomatous polyposis coli (APC), and -catenin. In contrast, the noncanonical Wnt signaling pathway has two intracellular signaling cascades that consist of the Wnt/ Ca2+ pathway with protein kinase C (PKC) and the Wnt/PCP pathway involving Rho/Rac small GTPase and Jun N-terminal kinase (JNK). Through a series of signaling pathways, Wnt proteins modulate cell development, proliferation, and cell fate. In regards to cell survival and fate through PCD, Wnt may be critical for the prevention of tissue pathology that involves cytokine and growth factor control during disorders such as neuropsychiatric disease, retinal disease, and Alzheimer's disease. Elucidation of the vital elements that shape and control the Wnt-Frizzled signaling pathway may provide significant prospects for the treatment of disorders of the nervous system.

Keywords: adenomatous polyposis coli; akt; alzheimers; b-catenin; dishevelled; erythropoietin; frizzled; gsk-b; neurons; psychiatric

Document Type: Review article

DOI: http://dx.doi.org/10.2174/156720205774322557

Affiliations: 1: Department of Neurology, 8C-1 UHC, Wayne State University School of Medicine, 4201 St. Antoine, Detroit, MI 48201, USA.

Publication date: 2005-10-01

More about this publication?

• Current Neurovascular Research (CNR) provides a cross platform for the publication of scientifically rigorous research that addresses disease mechanisms of both neuronal and vascular origins in neuroscience. The journal serves as an international forum for the publication of novel and pioneering original work as well as timely neuroscience research reviews in the disciplines of cell developmental disorders, plasticity, and degeneration that bridge the gap between basic science research and clinical discovery. CNR emphasizes the elucidation of disease mechanisms, both cellular and molecular, which can impact the development of unique therapeutic strategies for neuronal and vascular disorders.

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