Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
free
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
free free
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve Pubget Overpricing |
lüll Mutations in TDP-43 link glycine-rich domain functions to amyotrophic lateral sclerosis Pesiridis GS; Lee VM; Trojanowski JQHum Mol Genet 2009[Oct]; 18 (R2): R156-62Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease that affects approximately 2/100,000 individuals each year worldwide. Patients with ALS suffer from rapidly progressive degeneration of motor neurons ultimately leading to death. The major pathological features observed in post-mortem tissue from patients with ALS are motor neuron loss, cortical spinal tract degeneration, gliosis and cytoplasmic neuronal inclusions formed by TDP-43 or TAR DNA binding Protein with a molecular mass of 43 kDa, which are now recognized as the signature lesions of sporadic ALS. TDP-43 possesses two RNA binding domains (RBD) and a glycine-rich C terminus classifying it with other heterogeneous nuclear ribonucleoproteins known as 2XRBD-Gly proteins. A number of reports showed that a subset of patients with ALS possess mutations in the TDP-43 (TARDBP) gene. This further strengthens the hypotheses that gain of toxic function or loss of function in TDP-43 causes ALS. Currently, 29 different TARDBP missense mutations have been reported in 51 unrelated sporadic or familial ALS cases and two cases of ALS plus concomitant frontotemporal lobar degeneration with a remarkable concentration of mutations in the C-terminal glycine-rich domain of TDP-43. As these mutations will most certainly be an invaluable tool for the design and implementation of ALS animal and cell models, as well as serve as a platform for exploring the pathobiology of TDP-43, here we summarize the identified pathogenic TARDBP mutations and their potential impact on our understanding of the role of TDP-43 in disease.|Amino Acid Sequence[MESH]|Amyotrophic Lateral Sclerosis/*genetics/pathology[MESH]|DNA-Binding Proteins/*chemistry/*genetics[MESH]|Glycine/*metabolism[MESH]|Humans[MESH]|Immunohistochemistry[MESH]|Molecular Sequence Data[MESH]|Mutation/*genetics[MESH]|Protein Structure, Tertiary[MESH] |