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 inembryonic and adult life. Specifically, the Wnt/beta-catenin axis is pivotal to the development and homeostasisof the nervous system, and its dysregulation has been associated with various neurological10 disorders, including neurodegenerative diseases. Therefore, this signaling pathway has been proposedas a potential therapeutic target against neurodegeneration.AREAS COVERED: This review focuses on the role of Wnt/beta-catenin pathway in the pathogenesis ofneurodegenerative diseases, including Parkinson's and Alzheimer's Diseases, and Amyotrophic LateralSclerosis. The evidence showing that defects in the signaling might be involved in the development of15 these diseases, and the pharmacological approaches tested so far, are discussed. The possibilities thatthis 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 ofneurodegenerative diseases demonstrates how targeting this signaling for therapeutic purposes couldbe a great opportunity for both neuroprotection and neurorepair. Without overlooking some licit20 concerns about drug safety and delivery to the brain, there is growing and more convincing evidencethat restoring this signaling in neurodegenerative diseases may strongly increase the chance to developdisease-modifying treatments for these brain pathologies.