A Two-Clone Approach to Study Signaling Interactions among Neuronal Cells in a Pre-clinical Alzheimer's Disease Model
Catherine J. Yeates,
Ankita Sarkar,
Prajakta Deshpande,
Madhuri Kango-Singh,
Amit Singh
Affiliations
Catherine J. Yeates
Department of Biology, University of Dayton, Dayton, OH 45469, USA
Ankita Sarkar
Department of Biology, University of Dayton, Dayton, OH 45469, USA
Prajakta Deshpande
Department of Biology, University of Dayton, Dayton, OH 45469, USA
Madhuri Kango-Singh
Department of Biology, University of Dayton, Dayton, OH 45469, USA; Premedical Program, University of Dayton, Dayton, OH 45469, USA; Center for Tissue Regeneration and Engineering at Dayton (TREND), University of Dayton, Dayton, OH 45469, USA; The Integrative Science and Engineering Center, University of Dayton, Dayton, OH 45469, USA
Amit Singh
Department of Biology, University of Dayton, Dayton, OH 45469, USA; Premedical Program, University of Dayton, Dayton, OH 45469, USA; Center for Tissue Regeneration and Engineering at Dayton (TREND), University of Dayton, Dayton, OH 45469, USA; The Integrative Science and Engineering Center, University of Dayton, Dayton, OH 45469, USA; Center for Genomic Advocacy (TCGA), Indiana State University, Terre Haute, IN, USA; Corresponding author
Summary: To understand the progression of Alzheimer's disease, studies often rely on ectopic expression of amyloid-beta 42 (Aβ42) throughout an entire tissue. Uniform ectopic expression of Aβ42 may obscure cell-cell interactions that contribute to the progression of the disease. We developed a two-clone system to study the signaling cross talk between GFP-labeled clones of Aβ42-expressing neurons and wild-type neurons simultaneously generated from the same progenitor cell by a single recombination event. Surprisingly, wild-type clones are reduced in size as compared with Aβ42-producing clones. We found that wild-type cells are eliminated by the induction of cell death. Furthermore, aberrant activation of c-Jun-N-terminal kinase (JNK) signaling in Aβ42-expressing neurons sensitizes neighboring wild-type cells to undergo progressive neurodegeneration. Blocking JNK signaling in Aβ42-producing clones restores the size of wild-type clones.
