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Review
. 2008 Jul;8(7):969-78.
doi: 10.1517/14712598.8.7.969.

TDP-43 in neurodegenerative disorders

Casey Cook  1 , Yong-jie Zhang, Ya-fei Xu, Dennis W Dickson, Leonard Petrucelli
Affiliations
Review

TDP-43 in neurodegenerative disorders

Casey Cook et al. Expert Opin Biol Ther. 2008 Jul.

Abstract

Background: The number of neurodegenerative diseases associated with pathological aggregates of transactivation response element (TAR)-DNA-binding protein 43 (TDP-43) has increased, leading to the new designation 'TDP-43 proteinopathy.' Biochemically, TDP-43 proteinopathies are characterized by decreased solubility, hyperphosphorylation, and cleavage of TDP-43 into 25- and 35-kDa fragments, and by altered cellular localization.

Objective: This review summarizes research characterizing the distribution of TDP-43 pathology in human postmortem brain tissue and discusses possible therapeutic strategies based on genetic and in vitro studies.

Methods: We reviewed recent studies of TDP-43 proteinopathy.

Results/conclusion: Given that several different mutations can lead to TDP-43 proteinopathies, including mutations in progranulin and valosin-containing protein, research is needed to decipher and potentially exploit the link between these mutations and TDP-43 pathology.

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Figures

Figure 1
Figure 1
Schematic of TDP-43 Molecule
Figure 2
Figure 2
Cortex (a, b & c) and dentate gyrus (d, e & f) of Type 1 (a & d), Type 2 (b & e), and Type 3 (c & f) FTLD-U according to Sampathu & Cairns [1]. Type 1. Predominance of dystrophic neurites (DN) (a, inset) in cortex with round neuronal cytoplasmic inclusions (NCI) (d, inset) in the dentate gyrus. Type 2. Predominance of NCI, including granular cytoplasmic TDP-43 immunoreactivity, with sparse DN in cortex (b, inset) and dentate gyrus (e, inset). Type 3. NCI, DN & neuronal intranuclear inclusions (NII) (c, inset) and NCI and NII in dentate gyrus (f, inset).
See this image and copyright information in PMC

References

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