What does TARDBP stand for?
TARDBP (TAR DNA Binding Protein) is a Protein Coding gene. Diseases associated with TARDBP include Amyotrophic Lateral Sclerosis 10 With Or Without Frontotemporal Dementia and Frontotemporal Dementia And/Or Amyotrophic Lateral Sclerosis 1.
What is the TARDBP gene?
The TARDBP gene provides instructions for making a protein called transactive response DNA binding protein 43 kDa (TDP-43). This protein is found within the cell nucleus in most tissues and is involved in many of the steps of protein production.
What chromosome is the TARDBP gene on?
It is encoded by the TARDBP gene on chromosome 1, and contains a nuclear-localization signal, two RNA-binding motifs, and a glycine-rich region, which contains a “prion-like” domain and mediates protein and heterogeneous nuclear ribonucleoproteins (hnRNP) interactions.
What does TDP 43 stand for?
TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa), is a protein that in humans is encoded by the TARDBP gene.
How does C9orf72 cause ALS?
In ALS, the large size of motor neurons is thought to make these cells vulnerable to impairments in normal cell function. Disruptions in C9orf72 protein function may lead to premature motor neuron cell death, resulting in the signs and symptoms of ALS.
What causes TDP-43?
Mutations of the nuclear localization sequence (NLS) in the NTD are the cause of cytoplasmic localization and aggregation of TDP-4334 (Fig. 1). TDP-43 contains two RRM domains that comprise five β-strands and two α-helices.
Is TDP-43 a prion?
Recent studies have shown that, like tau and α-synuclein, TAR-DNA binding protein of 43 kDa (TDP-43) can form aggregates in vitro in a seed-dependent, self-templating, prion-like manner.
What is FTLD TDP?
Introduction. Frontotemporal lobar degeneration (FTLD) with TDP-43 inclusions (FTLD-TDP) exhibits considerable pathologic, clinical and genetic heterogeneity [16].
Does everyone have the C9orf72 gene?
C9orf72 is present in approximately 40% of familial ALS and 8-10 % of sporadic ALS. It is currently the most common demonstrated mutation related to ALS – far more common than SOD1 or TDP-43.
What is the function of C9orf72?
The C9orf72 gene provides instructions for making a protein that is found in various tissues. The protein is abundant in nerve cells (neurons) in the outer layers of the brain (cerebral cortex) and in specialized neurons in the brain and spinal cord that control movement (motor neurons).
Where is TDP-43 found?
In normal cells, TDP-43 is mainly present in the nucleus and plays important roles in RNA regulation, such as transcriptional regulation, alternative splicing, and mRNA stabilization11,12,13. Under pathological conditions, cleavage, hyperphosphorylation and ubiquitination of TDP-43 can occur14,15,16.
What proteins aggregate in ALS?
The neuromuscular disorder amyotrophic lateral sclerosis (ALS) is characterized by protein inclusions formed by either TAR DNA-binding protein of 43 kDa (TDP-43), Cu/Zn superoxide dismutase (SOD1), or fused in sarcoma (FUS), in both upper and lower motor neurons.