Jan 1, 2014

TDP-43-The key to understanding amyotrophic lateral sclerosis

Rare Diseases
Zuo-Shang Xu, Chunxing Yang

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes motor neuron degeneration leading to progressive muscle atrophy, weakness, paralysis and death. The majority of ALS (>95%) shows intracellular aggregation of transactive response DNA binding protein (TDP-43) as a prominent pathological feature. TDP-43 is normally a nuclear protein. In ALS, TDP-43 accumulates and aggregates in the cytoplasm (thus forming TDP-43 proteinopathy) and is depleted from the nucleus in CNS cells, including motor neurons and glia. While TDP-43 aggregation can harm cells through a gain of toxicity, it can also cause a loss of TDP-43 function in conjunction with its nuclear depletion. TDP-43 regulates its own expression to maintain itself at a constant level. Perturbation of this level by either increasing or decreasing TDP-43 in animal models leads to neurodegeneration and ALS phenotypes. The evidence supports the hypothesis that TDP-43 dysfunction is a critical driver of neurodegeneration in the vast majority of ALS cases.

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Mentioned in this Paper

TARDBP
Cessation of Life
Nerve Degeneration
Neuroglia
Motor Neurons
Cell Nucleus
Amyotrophic Lateral Sclerosis
Protein TDP-43
Toxic Effect
Muscular Atrophy

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