Tryptamine-Induced Tryptophanyl-tRNAtrp Deficiency in Neurodifferentiation and Neurodegeneration Interplay: Progenitor Activation with Neurite Growth Terminated in Alzheimer's Disease Neuronal Vesicularization and Fragmentation
Abstract
Tryptophanyl-tRNA synthetase (TrpRS) catalyzes tryptophanyl-tRNAtrp formation. At concentrations exceeding tryptophan, tryptamine inhibits TrpRS. This leads in tryptophanyl-tRNA deficiency and synthesis of aberrant proteins. Tryptamine presents in food and crosses blood-brain barrier. The purpose of this study is to test the hypothesis that tryptamine-induced changes in cell and animal models correlate with Alzheimer's disease (AD) manifestations. Tryptamine prevented growth of human neuroblastoma. Epithelioids recovered growth in tryptamine-free medium, while neuroblasts died. Tryptamine induced epithelioid differentiation forming synaptic vesicles, neuritic contacts, and TrpRS+ axons in stable sublines. A fraction of epithelioids was adhered to satellite cells via trypsin-resistant interdigitating junctions. Tryptamine stimulated satellite division and differentiation into neurons, transitional cell variants and neuroblasts able to repopulate. Both tryptamine-inhibited and hypoxia-downregulated TrpRS translocates into cytoplasmic extensions. TrpRS is secreted into extracellular space as a free protein or within vesicles extended from cytoplasm and then pinched-off from plasma membrane of tryptamine-treated cells. Extracellular vesicles fuse in congophilic TrpRS+ plaques in tryptamine-treated culture and AD brain. TrpRS prominent immunoreactivity is associated with plasma and vesicle membranes of satellites and AD brain degenerated neurons. Tryptamine-modified mouse brain ex…
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Only NT1-lipidoids could effectively facilitate crossing of the BBB, whereas NT2-lipidoids could not, despite both tryptamine and phenethylamine crossing the BBB.
“While both tryptamine (NT1) and phenethylamine (NT2) can cross the BBB (33, 34), only NT1-lipidoids could effectively facilitate crossing of the BBB.”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [33]
Tryptamine and phenethylamine can effectively cross the BBB via active transport.
“These precursors were selected, in part, due to the compelling evidence in the literature that tryptamine and phenethylamine can effectively cross the BBB via active transport (33, 34).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [33]
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Ma, F., Yang, L., Sun, Z., Chen, J., Rui, X., Glass, Z., & Xu, Q. (2020) · Science Advances · doi:10.1126/sciadv.abb4429 · Cited by 218 · see citing works
- Authors
- Paley, E. L.
- Affiliations
- Nova Southeastern University (US)
- Corresponding author
- Paley, Elena L.
- ORCID
- Paley, Elena L.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2011-09-09
- Volume
- 26
- Issue
- 2
- Pages
- 263-298
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1542533815
- Cited by
- 35
- References
- 0
- Citations by year
- 2024: 12 · 2023: 10 · 2021: 5 · 2020: 1 · 2019: 2 · 2018: 4
- FWCI
- 0.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tryptamine, tryptophanyl-tRNA synthetase
- MeSH terms
- Animals, Humans, Nerve Degeneration, Neurons, Tryptamines, Tryptophan-tRNA Ligase, Neurites, Cell Line, Tumor, Mice, Neurogenesis
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