TARDBP Specific Neutra™ Antibody Products

As we know, HIV-1 is responsible for acquired immunodeficiency syndrome (AIDS). The virus possesses an RNA genome that undergoes conversion into chromosomally integrated DNA during replication. TARDBP is a transcriptional repressor and binds to the chromosomally integrated TAR DNA, thereby suppressing HIV-1 transcription. Additionally, TARDBP serves as an RNA-binding protein, participating in diverse aspects of RNA biogenesis and processing.

Its Gene ID: 23435, UniProtKB ID: Q13148, and OMIM ID: 605078.

Involved Pathway of TARDBP

TARDBP, an RNA-binding protein, is strongly implicated in the pathogenesis of several neurodegenerative conditions, including frontotemporal dementia. Extensive research has investigated various cellular functions' involvement in disease progression, with nucleocytoplasmic transport, protein homeostasis, RNA interactions, and cellular stress emerging as potential contributors to the onset of TARDBP pathology. Elevated protein concentration or cellular stress can lead to the formation of ubiquitinated phosphorylated aggregates of cytoplasmic TARDBP.

Fig.1 Regulatory mechanisms involved in maintaining cellular TDP-43 (TARDBP).¹

Harnessing Anti-TARDBP Antibodies for Neurodegenerative Disorders

The majority of cases exhibit cytoplasmic inclusions of the multifunctional RNA-binding protein TARDBP in both neurons and glial cells. While TARDBP is primarily localized in the nucleus, where it plays a dominant role in mRNA splicing and gene expression regulation, its abnormal cytoplasmic accumulation is characteristic of disease pathology. Monoclonal antibodies targeting the glycine-rich domain have shown efficacy in inhibiting disease-associated phase separation and aggregation of TARDBP in vitro, as well as in suppressing aggregate uptake in cells. This novel mechanism of action for antibody therapy alters the phase separation properties of disease-linked proteins.

• Therapeutic Approach with Anti-TARDBP Antibodies for TARDBP Proteinopathies

Cytoplasmic aggregation and subsequent nuclear depletion of the RNA-binding protein TARDBP characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar (FTD) degeneration. Immunization using a C-terminal peptide containing disease-associated phospho-serines leads to a significant reduction in serum neurofilament light chain levels, suggesting decreased neuroaxonal damage. Furthermore, recently developed monoclonal antibodies directed against the glycine-rich domain efficiently are reported to attenuate the phase separation and aggregation of TARDBP, concurrently impeding the cellular uptake of pre-existing aggregates. By focusing on either active or passive immunization, the targeting of the RRM2 domain and the C-terminal region of TARDBP shows potential for therapeutic intervention in TARDBP proteinopathies, disrupting pivotal pathways involved in disease progression.

Fig.2 Inhibition of TDP-43 (TARDBP) aggregation and reduction of neurofilament levels through glycine-rich domain targeting with antibodies.²

• Exploring TARDBP Interactions in Neurodegenerative Diseases

TARDBP aggregation in Alzheimer's disease (AD) arises despite its predominant nuclear localization as an RNA/DNA binding protein (RBP). While typically found in the nucleus, TARDBP has been observed in stress granules in FTD and ALS pathologies, along with several other RBPs. The presence of TARDBP oligomers in human brain tissues affected by ALS, FTD, and AD has been noted. Utilizing novel antibodies targeting TARDBP oligomers, as well as generic TARDBP antibodies, could elucidate the potential cross-seeding effect of TARDBP oligomers from AD, ALS, and FTD brains on tau aggregation. These findings suggest potential implications of TARDBP/tau interactions in AD, ALS, and FTD.

Creative Biolabs provides an extensive range of various meticulously engineered anti-TARDBP antibody products, crafted using recombinant techniques. Additionally, customization options are available to tailor TARDBP-based monoclonal antibodies to suit specific requirements.

REFERENCES

1. Chen, Han-Jou, and Jacqueline C. Mitchell. "Mechanisms of TDP-43 proteinopathy onset and propagation." International Journal of Molecular Sciences 22.11 (2021): 6004.
2. Riemenschneider, Henrick, et al. "Targeting the glycine-rich domain of TDP-43 with antibodies prevents its aggregation in vitro and reduces neurofilament levels in vivo." Acta Neuropathologica Communications 11.1 (2023): 112.