Normal Molecular Specification and Neurodegenerative Disease-Like Death of Spinal Neurons Lacking the SNARE-Associated Synaptic Protein Munc18-1.
Chris LawMarcos Schaan ProfesMartin LevesqueJulia A KaltschmidtMatthijs VerhageArtur KaniaPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
In this work, we demonstrate the absence of a requirement for regulated neurotransmitter release in the assembly of early neuronal circuits by assaying transcriptional identity, axon growth and guidance, and mRNA expression in Munc18-1-null mice. Furthermore, we characterize the neurodegeneration observed in Munc18-1 mutants and demonstrate that this cell-autonomous process does not appear to be a result of defects in growth factor signaling or ER stress caused by protein trafficking defects. However, we find the presence of various pathological hallmarks of Alzheimer's disease that suggest parallels between the degeneration in these mutants and neurodegenerative conditions.
Keyphrases
- growth factor
- spinal cord
- transcription factor
- protein protein
- wild type
- gene expression
- single cell
- binding protein
- amino acid
- stem cells
- metabolic syndrome
- insulin resistance
- high fat diet induced
- spinal cord injury
- oxidative stress
- skeletal muscle
- small molecule
- heat shock
- optical coherence tomography
- blood brain barrier
- endoscopic submucosal dissection