TAR DNA-binding protein messenger RNA (TARDBP mRNA)

TARDBP mRNA is the messenger RNA transcript that encodes the TAR DNA-binding protein 43 (TDP-43), a critical RNA-binding protein involved in the regulation of transcription, alternative splicing, and mRNA stability [UniProt P06748, NCBI Gene ID: 23435]. Under normal physiological conditions, TDP-43 primarily resides in the nucleus, but in pathological states such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), the protein forms toxic cytoplasmic aggregates and disappears from the nucleus, a phenomenon known as TDP-43 proteinopathy [Nature Reviews Neurology, 2017]. Therapeutic strategies focusing on TARDBP mRNA utilize antisense oligonucleotides (ASOs) or RNA interference to lower mRNA levels and subsequently reduce the production of aggregate-prone protein [PubMed: 25681023]. However, because TDP-43 is essential for cellular homeostasis, therapeutic interventions must carefully balance the reduction of toxic aggregates with the maintenance of sufficient functional protein to avoid neurotoxic loss-of-function effects [Nature Communications, 2019]. Current research is directed toward optimizing delivery to the central nervous system and refining the specificity of knockdown to treat ALS, FTD, and related conditions like Limbic-predominant age-related TDP-43 encephalopathy (LATE) [The Lancet Neurology, 2019].

Other names

TDP-43 mRNATDP43 mRNATAR DNA-binding protein 43 transcript

Antisense oligonucleotide-mediated mRNA degradation via RNase H recruitment or steric hindrance of translation to modulate TDP-43 protein levels.