An Exploration of the Coherent Effects between METTL3 and NDUFA10 on Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized primarily by a decline in cognitive function. However, the etiopathogenesis of AD is unclear. N6-methyladenosine (m6A) is abundant in the brain, and it is interesting to explore the relationship between m6A and AD causes. In this paper, the gene expression of METTL3 and NDUFA10 were found to correlate with the Mini-mental State Examination (MMSE), which is a clinical indicator of the degree of dementia. METTL3 is involved in post-transcriptional methylation and the formation of m6A. NDUFA10 encodes the protein with NADH dehydrogenase activity and oxidoreductase activity in the mitochondrial electron transport chain. The following three characteristics were observed in this paper: 1. The lower the expression level of NDUFA10, the smaller the MMSE, and the higher the degree of dementia. 2. If the expression level of METTL3 dropped below its threshold, the patient would have a risk of AD with a probability close to 100%, suggesting a basic necessity for m6A to protect mRNA. 3. The lower the expression levels of both METTL3 and NDUFA10, the more likely the patient would suffer from AD, implying the coherence between METTL3 and NDUFA10. Regarding the above discovery, the following hypothesis is presented: METTL3 expression level is downregulated, then the m6A modification level of NDUFA10 mRNA is also decreased, thereby reducing the expression level of NDUFA10-encoded protein. Furthermore, the abnormal expression of NDUFA10 contributes to the assembly disorder of mitochondrial complex I and affects the process of the electron respiratory chain, with the consequent development of AD. In addition, to confirm the above conclusions, the AI Ant Colony Algorithm was improved to be more suitable for discovering the characteristics of AD data, and the SVM diagnostic model was applied to mine the coherent effects on AD between METTL3 and NDUFA10. In conclusion, our findings suggest that dysregulated m6A leads to altered expression of its target genes, thereby affecting AD’s development.

The Features Analysis of Hemoglobin Expression on Visual Information Transmission Pathway in Early Stage of Alzheimer's Disease

“…Method: This paper includes both the methods the authors have used in the past year [43][44][45][46][47][48] and the new methods proposed in this paper. The new methods include the calculation of the correlation between different brain regions along the V-H pathway.…”

Emerging Roles for DNA 6mA and RNA m6A Methylation in Mammalian Genome

“…The m6A reader protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) was associated with extracellular matrix–receptor (ECM receptor) interaction, focal adhesion, cytokine–cytokine receptor interaction, and the TGF-β signaling pathways, and participated in the occurrence of AD [ 152 ]. In addition, NADH-ubiquinone oxidoreductase subunit A10 (NDUFA10) may be regulated via m6A modification, thereby affecting energy metabolism in AD [ 153 ].…”

The coherence between PSMC6 and α-ring in the 26S proteasome is associated with Alzheimer’s disease

“…Typical clinical manifestations of AD characterized by progressive impairment of episodic memory and cognitive function, eventually evolve into disruption of fundamental functions ( Long and Holtzman, 2019 ; Silva et al, 2019 ; Penney et al, 2020 ). Since the pathobiology of the disease is heterogeneous, clear pathogenesis remains elusive ( Scheltens et al, 2021 ; Zhang et al, 2022b ; Wenbo, 2023 ; Yang L. et al, 2023 ).…”