The role of microtubule proteins TUBB2A, TUBB3, and TUBB4B in neuronal dysfunction in Alzheimer’s disease: a bioinformatics analysis

Shu, Qi1,#; Liu, Ronghong1,#; Pang, Xinping2; Huang, Xudong3; Pang, Chaoyang1,*

1College of Computer Science, Sichuan Normal University, Chengdu, Sichuan Province, China

2School of Science, Xi’an Jiaotong-Liverpool University, Suzhou, Jiangsu Province, China

3Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA

*Correspondence to: Chaoyang Pang, MD, cypang@sicnu.edu.cn.

Abstract

Alzheimer’s disease represents a significant public health challenge, characterized by progressive cognitive decline and memory impairment. This study focuses on the roles of the microtubule proteins TUBB2A, TUBB3, and TUBB4B, which are critical components of β-tubulin and essential for guanosine triphosphate binding that promotes microtubule stability. Utilizing gene expression datasets from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), we conducted differential expression analysis and correlation assessments. Our results reveal significant downregulation of TUBB2A, TUBB3, and TUBB4B in Alzheimer’s disease, which correlates with the severity of neurofibrillary tangles and Mini-Mental State Examination scores. This study shows that the downregulation of β-tubulin inhibits tubulin assembly. From a dynamic perspective, it investigates the specific mechanisms by which β-tubulin genes such as TUBB2A, TUBB3, and TUBB4B contribute to Alzheimer’s disease. The research further explores the key roles of these β-tubulin genes in maintaining microtubule dynamic instability and functional integrity, which provides new insights for elucidating the molecular mechanisms underlying Alzheimer’s disease.

阿尔茨海默病神经功能障碍的分子机制：β微管蛋白TUBB2A，TUBB3和TUBB4B作用分析

摘要

阿尔茨海默病（Alzheimer's Disease，AD）是一种主要影响老年人的神经退行性疾病，以进行性认知衰退和记忆障碍为特征。此研究聚焦于微管蛋白TUBB2A，TUBB3和TUBB4B的作用，这些蛋白是β微管蛋白的关键组成部分，对鸟苷三磷酸结合至关重要，从而促进微管稳定性。利用美国国家生物技术信息中心基因表达综合数据库的基因表达数据集，进行了差异表达分析和相关性评估。结果显示，TUBB2A，TUBB3和TUBB4B在阿尔茨海默病中显著下调，且与神经原纤维缠结的严重程度及简易精神状态检查评分呈正相关。β微管蛋白的下调会抑制微管蛋白的组装。此研究进一步揭示了这些β微管蛋白基因在维持微管动态不稳定性和功能完整性中的关键作用，为阐明阿尔茨海默病的分子机制提供了新见解。