TARDBP, Pathologic TDP-43 and Motor Neuron Degeneration

Wed, 07/03/2013 - 12:41

The TARDBP gene codes for a transcriptional repressor protein known as TDP-43. The protein encoded by the TARDBP gene binds TAR DNA and functions to regulate translation. TDP-43 can also bind RNA which leads to transcriptional repression and the formation of splice variants encoding alternate forms of proteins. Additionally, the TARDBP gene plays an important role in mRNA transport. This gene is particularly active during fetal and neuronal development, where the rate of tissue production is very high.

Immunohistochemistry: TARDBP Antibody Immunohistochemistry: TARDBP Antibody

Mutations in the TARDBP gene are associated with the expression of aberrant forms of TDP-43 including the hyper-phosphorlated, ubiquitinated, cleaved form of TDP-43 is known as pathologic TDP-43. Pathologic TDP-43 is implicated in a number of disorders including frontal-temporal dementia, Parkinson’s disease, chronic traumatic encephalopathy resulting from head injury, and amyotrophic lateral sclerosis (ALS). 47 missense mutations have been described in a multitude of both familial and sporadic ALS cases. The majority of these mutations are located on the C-terminus of the proteins coded by TARDBP (1). Studies have suggested that certain TARDBP mutations result in the stabilization of the hTDP-43 polypeptide. High levels of this polypeptide evoke apoptotic cell death, consequently leading to neurodegeneration and the pathogenesis of ALS (2).

Recently, mutations of the TARDPB gene were also linked to toxicity in motor neurons, which results in characteristic motor neuron death in diseases like ALS. Motor neuron toxicity was examined in a study that was conducted on zebrafish in which a mutant human TARDPB gene was introduced to the specimen. The zebrafish in the study were born with curly tails and exhibited a delay to swim following a stimulus. The data from this study indicates that the motor neurons rather than the sensory neurons are affected by the mutation. Further analysis revealed shorter and more disorganized motor neuronal axons than the control, suggesting that TARDBP gene mutations directly contribute to the debilitating motor neuron degeneration that is typical of ALS (3).

  1. PMID: 23559573
  2. PMID: 23721326
  3. PMID: 19959528

Novus Biologicals offers various TARDBP reagents for your research needs including:


Written by Allie Wilson

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