1-L Transcription in Alzheimer's Disease

Overview

Journal Curr Issues Mol Biol

Publisher MDPI

Specialty Molecular Biology

Date 2022 Aug 25

PMID 36005139

Authors

Jozef Nahalka

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease is a very complex disease and better explanations and models are needed to understand how neurons are affected and microglia are activated. A new model of Alzheimer's disease is presented here, the β-amyloid peptide is considered an important RNA recognition/binding peptide. 1-L transcription revealed compatible sequences with AAUAAA (PAS signal) and UUUC (class III ARE rich in U) in the Aβ peptide, supporting the peptide-RNA regulatory model. When a hypothetical model of fibril selection with the prionic character of amyloid assemblies is added to the peptide-RNA regulatory model, the downregulation of the PI3K-Akt pathway and the upregulation of the PLC-IP3 pathway are well explained. The model explains why neurons are less protected from inflammation and why microglia are activated; why mitochondria are destabilized; why the autophagic flux is destabilized; and why the post-transcriptional attenuation of the axonal signal "noise" is interrupted. For example, the model suggests that Aβ peptide may post-transcriptionally control ELAVL2 (ELAV-like RNA binding protein 2) and DCP2 (decapping mRNA protein 2), which are known to regulate RNA processing, transport, and stability.

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