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. 2024 Nov 15;25(22):12268.
doi: 10.3390/ijms252212268.

The Fundamental Neurobiological Mechanism of Oxidative Stress-Related 4E-BP2 Protein Deamidation

Davis Joseph  1   2
Affiliations

The Fundamental Neurobiological Mechanism of Oxidative Stress-Related 4E-BP2 Protein Deamidation

Davis Joseph. Int J Mol Sci. .

Abstract

Memory impairment is caused by the absence of the 4E-BP2 protein in the brain. This protein undergoes deamidation spontaneously in the neurons. 4E-BP2 deamidation significantly alters protein synthesis in the neurons and affects the balance of protein production required for a healthy nervous system. Any imbalance in protein production in the nervous system causes neurodegenerative diseases. Discovering what causes 4E-BP2 deamidation will make it possible to control this balance of protein production and develop effective treatments against neurodegenerative diseases such as Alzheimer's and Parkinson's. The purpose of this work is to discover the neurobiological mechanism that causes the deamidation reaction in the 4E-BP2 protein by performing immunoblotting in the retinal ganglia, the optic nerve, the dorsal root ganglia, the sciatic nerve, and the whole brain, extracted via dissection from 2-month-old, Wild-type male mice. The results show that axons and their unique properties cause neuron-specific 4E-BP2 deamidation in the nervous system, confirming conclusively that axons are the critical factors behind the fundamental neurobiological mechanism of 4E-BP2 protein deamidation.

Keywords: 4E-BP2; Alzheimer’s; Parkinson’s; deamidation; neurodegeneration; oxidative stress.

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Conflict of interest statement

Flogen Technologies Inc. employed Davis Joseph. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Flogen Technologies Inc. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.

Figures

Figure 1
Figure 1
4E-BP2 western blot of the whole brain, the optic nerve, and the retinal ganglia from 2-month-old WT mice, using GAPDH as the control: (A) Immunoblotting data. (B) Bonferroni multiple comparisons test of the deamidation ratios of the three organs studied. The star (“*”) between columns symbolizes a significant difference with a p-value of less than 0.05 between results, whereas “ns” stands for “not significant”. Three stars (“***”) between columns symbolize a significant difference with a p-value of less than 0.001 between results. More stars mean a more substantial difference between results.
Figure 2
Figure 2
4E-BP2 western blot of the sciatic nerve and the dorsal root ganglia (DRG) from 2-month-old WT mice, using GAPDH as the control: (A) Immunoblotting data. (B) T-test comparing the two organs’ deamidation ratios. Three stars (“***”) between columns symbolize a significant difference between results with a p-value of less than 0.001.
Figure 3
Figure 3
T-test comparison between the deamidation ratios of the whole brain and the sciatic nerve. Four stars (“****”) between columns symbolize a significant difference between results with a p-value of less than 0.0001.
Figure 4
Figure 4
Six-step chemical reaction of deamidation occurring in 4E-BP2 at positions N99 and N102.
Figure 5
Figure 5
Biochemical flow sheet of the impact of the axon on protein production in the mammalian organism (all images used are royalty-free, except for the 5′ cap structure image, which the author made, and the 4E-BP and eIF4E images obtained using AlphaFold [47,48,49]).
See this image and copyright information in PMC

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