RT Journal Article
T1 Synaptic Regulator α-Synuclein in Dopaminergic Fibers Is Essentially Required for the Maintenance of Subependymal Neural Stem Cells.
A1 Perez-Villalba, Ana
A1 Sirerol-Piquer, M Salomé
A1 Belenguer, Germán
A1 Soriano-Cantón, Raúl
A1 Muñoz-Manchado, Ana Belén
A1 Villadiego, Javier
A1 Alarcón-Arís, Diana
A1 Soria, Federico N
A1 Dehay, Benjamin
A1 Bezard, Erwan
A1 Vila, Miquel
A1 Bortolozzi, Analía
A1 Toledo-Aral, Juan José
A1 Pérez-Sánchez, Francisco
A1 Fariñas, Isabel
K1 Snca knock-out
K1 adult neurogenesis
K1 niche biology
K1 parkinsonism
K1 stemness
AB Synaptic protein α-synuclein (α-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinson's disease. Here, we report that α-SYN present in dopaminergic nigral afferents is essential for the normal cycling and maintenance of neural stem cells (NSCs) in the brain subependymal zone of adult male and female mice. We also show that premature senescence of adult NSCs into non-neurogenic astrocytes in mice lacking α-SYN resembles the effects of dopaminergic fiber degeneration resulting from chronic exposure to 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine or intranigral inoculation of aggregated toxic α-SYN. Interestingly, NSC loss in α-SYN-deficient mice can be prevented by viral delivery of human α-SYN into their sustantia nigra or by treatment with l-DOPA, suggesting that α-SYN regulates dopamine availability to NSCs. Our data indicate that α-SYN, present in dopaminergic nerve terminals supplying the subependymal zone, acts as a niche component to sustain the neurogenic potential of adult NSCs and identify α-SYN and DA as potential targets to ameliorate neurogenic defects in the aging and diseased brain.SIGNIFICANCE STATEMENT We report an essential role for the protein α-synuclein present in dopaminergic nigral afferents in the regulation of adult neural stem cell maintenance, identifying the first synaptic regulator with an implication in stem cell niche biology. Although the exact role of α-synuclein in neural transmission is not completely clear, our results indicate that it is required for stemness and the preservation of neurogenic potential in concert with dopamine.
YR 2017
FD 2017-12-07
LK http://hdl.handle.net/10668/11887
UL http://hdl.handle.net/10668/11887
LA en
DS RISalud
RD Apr 17, 2025