Niche-derived laminin-511 promotes midbrain dopaminergic neuron survival and differentiation through YAP
| Autor: | Enrique M. Toledo, Ernest Arenas, Shanzheng Yang, Carmen Saltó, Daniel Gyllborg, Dawei Zhang, J. Carlos Villaescusa |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival Cellular differentiation Dopamine Cell Cell Cycle Proteins Biology Biochemistry 03 medical and health sciences Mice Neural Stem Cells medicine Animals Humans skin and connective tissue diseases Molecular Biology Transcription factor Cells Cultured Adaptor Proteins Signal Transducing Regulation of gene expression Dopaminergic Neurons Dopaminergic Integrin alpha3beta1 PTEN Phosphohydrolase Brain Gene Expression Regulation Developmental Cell Differentiation Parkinson Disease YAP-Signaling Proteins Cell Biology Anatomy Embryo Mammalian Phosphoproteins Embryonic stem cell Neural stem cell Cell biology MicroRNAs 030104 developmental biology medicine.anatomical_structure nervous system Female Neuron Laminin |
| Zdroj: | Science signaling. 10(493) |
| ISSN: | 1937-9145 |
| Popis: | Parkinson’s disease (PD) is a neurodegenerative disorder in which the loss of dopaminergic neurons in the midbrain (mDA neurons) causes progressive loss of motor control and function. Using embryonic and mDA neurons, midbrain tissue from mice, and differentiated human neural stem cells, we investigated the mechanisms controlling the survival of mDA neurons. We found that the extracellular matrix protein laminin-511 (LM511) promoted the survival and differentiation of mDA neurons. LM511 bound to integrin α 3 β 1 and activated the transcriptional cofactor YAP. LM511-YAP signaling enhanced cell survival by inducing the expression of the microRNA miR-130a, which suppressed the synthesis of the cell death–associated protein PTEN. In addition, LM511-YAP signaling increased the expression of transcription factors critical for mDA identity, such as LMX1A and PITX3, and prevented the loss of mDA neurons in response to oxidative stress, a finding that warrants further investigation to assess therapeutic potential for PD patients. We propose that by enhancing LM511-YAP signaling, it may be possible to prevent mDA neuron degeneration in PD or enhance the survival of mDA neurons in cell replacement therapies. |
| Databáze: | OpenAIRE |
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