Understanding age-related pathologic changes in TDP-43 functions and their consequence on RNA splicing and signalling in health and disease

Ageing Res Rev. 2024 Feb 22:102246. doi: 10.1016/j.arr.2024.102246. Online ahead of print.ABSTRACTTAR DNA binding protein-43 (TDP-43) is a key component in RNA splicing which plays a crucial role in the aging process. In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Limbic-predominant age-related TDP-43 Encephalopathy (LATE), TDP-43 can be mutated, mislocalised out of the nucleus of neurons and glial cells and form cytoplasmic inclusions. These TDP-43 alterations can lead to its RNA splicing dysregulation and contribute to mis-splicing of various types of RNA, such as mRNA, microRNA, and circRNA. These changes can result in the generation of an altered transcriptome and proteome within cells, ultimately changing the diversity and quantity of gene products. In this review, we summarise the findings of novel atypical RNAs resulting from TDP-43 dysfunction and their potential biomarkers or targets for therapeutic development.PMID:38401571 | DOI:10.1016/j.arr.2024.102246

Source: Ageing Research Reviews - February 24, 2024 Category: Genetics & Stem Cells Authors: Flora Cheng Tyler Chapman Selina Zhang Marco Morsch Roger Chung Albert Lee Stephanie L Rayner Source Type: research