Targeting the Wnt/beta-catenin pathway in neurodegenerative diseases: recent approaches and current challenges

INTRODUCTION: Wnt/beta-catenin signaling is an evolutionarily conserved pathway having a crucial role in embryonic and adult life. Specifically, the Wnt/beta-catenin axis is pivotal to the development and homeostasis of the nervous system, and its dysregulation has been associated with various neurological 10 disorders, including neurodegenerative diseases. Therefore, this signaling pathway has been proposed as a potential therapeutic target against neurodegeneration. AREAS COVERED: This review focuses on the role of Wnt/beta-catenin pathway in the pathogenesis of neurodegenerative diseases, including Parkinson's and Alzheimer's Diseases, and Amyotrophic Lateral Sclerosis. The evidence showing that defects in the signaling might be involved in the development of 15 these diseases, and the pharmacological approaches tested so far, are discussed. The possibilities that this pathway offers in terms of new therapeutic opportunities are also considered. EXPERT OPINION: The increasing interest paid to the role of Wnt/beta-catenin pathway in the onset of neurodegenerative diseases demonstrates how targeting this signaling for therapeutic purposes could be a great opportunity for both neuroprotection and neurorepair. Without overlooking some licit 20 concerns about drug safety and delivery to the brain, there is growing and more convincing evidence that restoring this signaling in neurodegenerative diseases may strongly increase the chance to develop disease-modifying treatments for these brain pathologies.