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Translation of WNT developmental programs into stem cell replacement strategies for the treatment of Parkinson's disease
Author(s) -
Toledo Enrique M,
Gyllborg Daniel,
Arenas Ernest
Publication year - 2017
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13871
Subject(s) - wnt signaling pathway , neuroscience , biology , induced pluripotent stem cell , parkinson's disease , stem cell , disease , bioinformatics , signal transduction , embryonic stem cell , medicine , microbiology and biotechnology , genetics , pathology , gene
Wnt signalling is a highly conserved pathway across species that is critical for normal development and is deregulated in multiple disorders including cancer and neurodegenerative diseases. Wnt signalling is critically required for midbrain dopaminergic (mDA) neuron development and maintenance. Understanding the molecular processes controlled by Wnt signalling may thus hold the key to understand the physiopathology and to develop novel therapies aimed at preventing the loss of mDA neurons in Parkinson's disease (PD). Pharmacological tools to activate Wnt signalling have been used to translate in vivo developmental processes into protocols for the generation of bona fide mDA neurons from human pluripotent stem cells. Moreover, these protocols are currently being fine-tuned to generate mDA neurons for clinical trials in PD. At the same time, a vast amount of molecular details of Wnt signalling continues to emerge and remains to be implemented into new protocols. We hereby review novel pharmacological tools to activate Wnt signalling and how single-cell RNA-sequencing is contributing to unravel the complexity of this pathway in the developing human ventral midbrain, generating novel hypotheses and identifying new players and opportunities to further improve cell replacement therapy for PD.