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Amyloid Beta Selectively Modulates Neuronal Trkb Alternative Transcript Expression With Implications For Alzheimer's Disease, J Wong, M Higgins, G Halliday, B Garner
Amyloid Beta Selectively Modulates Neuronal Trkb Alternative Transcript Expression With Implications For Alzheimer's Disease, J Wong, M Higgins, G Halliday, B Garner
Illawarra Health and Medical Research Institute
Dysregulation in brain-derived neurotrophic factor (BDNF)/full-length TrkB (TrkB-TK+) signaling is implicated in promoting neurodegeneration in Alzheimer's disease (AD). BDNF/TrkB-TK+ signaling can be modulated by the presence of truncated TrkB isoforms (TrkB-TK-, TrkB-Shc). All TrkB isoforms are encoded by different alternative transcripts. In this study, we assessed if expression of the three main TrkB alternative transcripts, TrkB-TK+, TrkB-TK-, and TrkB-Shc are altered in AD. Using a cohort of control and AD brains (n=29), we surveyed the hippocampus, temporal cortex, occipital cortex, and cerebellum and found specific increases in TrkB-Shc, a neuron-specific transcript, in the AD hippocampus. No significant changes were detected …
Srp20 Regulates Trkb Pre-Mrna Splicing To Generate Trkb-Shc Transcripts With Implications For Alzheimer's Disease, Jenny Wong, Brett Garner, Glenda M. Halliday, John B.J Kwok
Srp20 Regulates Trkb Pre-Mrna Splicing To Generate Trkb-Shc Transcripts With Implications For Alzheimer's Disease, Jenny Wong, Brett Garner, Glenda M. Halliday, John B.J Kwok
Illawarra Health and Medical Research Institute
Previously, we reported elevated levels of the neuronspecific tropomyosin receptor kinase B (TrkB) transcript, TrkB- sarc homology containing (Shc) in the hippocampus of Alzheimer’s disease (AD) brains. In this study, we determined how TrkB-Shc transcripts are increased in AD. Utilizing a TrkB minigene transiently transfected into SHSY5Y cells, we found increased exon 19 inclusion in TrkB minigene transcripts (to generate TrkB-Shc) following cellular exposure to amyloid beta 1–42 (Ab42). As this suggested altered TrkB pre-mRNA splicing in AD, we conducted an in silico screening for putative splice regulatory protein-binding sites in the intron/exon splice regulatory regions of exons 18 and …