Journal
NEUROMOLECULAR MEDICINE
Volume 9, Issue 1, Pages 55-82Publisher
HUMANA PRESS INC
DOI: 10.1385/NMM:9:1:55
Keywords
Alzheimer's disease; neurodegeneration; neurofibrillary tangles; tryptamine; tryptophanyl-tRNA synthetase
Categories
Funding
- NIBIB NIH HHS [EB01850] Funding Source: Medline
Ask authors/readers for more resources
The neuropathological hallmarks of Alzheimer's disease (AD) and other taupathies include neurofibrillary tangles and plaques. Despite the fact that only 2-10% of AD cases are associated with genetic mutations, no nontransgenic or metabolic models have been generated to date. The findings of tryptophanyl-tRNA synthetase (TrpRS) in plaques of the AD brain were reported recently by the authors. Here it is shown that expression of cytoplasmic-TrpRS is inversely correlated with neurofibrillary degeneration, whereas a nonionic detergent-insoluble presumably aggregated TrpRS is simultaneously accumulated in human cells treated by tryptamine, a metabolic tryptophan analog that acts as a competitive inhibitor of TrpRS. TrpRSN-terminal peptide self-assembles in double-helical fibrils in vitro. Herein, tryptamine causes neuropathy characterized by motor and behavioral deficits, hippocampal neuronal loss, neurofibrillary tangles, amyloidosis, and glucose decrease in mice. Tryptamine induced the formation of helical fibrillary tangles in both hippocampal neurons and glia. Taken together with the authors' previous findings of tryptamine-induced nephrotoxicity and filamentous tangle formation in kidney cells, the authors' data indicates a general role of tryptamine in cell degeneration and loss. It is concluded that tryptamine as a component of a normal diet can induce neurodegeneration at the concentrations, which might be consumed along with food. Tryptophan-dependent tRNA(trp) aminoacylation catalyzed by TrpRS can be inhibited by its
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available