TDP-43 in neurodegenerative disorders.
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.


CONCLUSIONS
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.
Mayo Clinic, 4500 San Pablo Road Jacksonville, Florida 32224, USA.
Casey
C
Cook
Yong-jie
YJ
Zhang
Ya-fei
YF
Xu
Dennis W
DW
Dickson
Leonard
L
Petrucelli
D000251:Adenosine Triphosphatases / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D016501:Neurites / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D000077153:Progranulins; D020218:Response Elements; D012995:Solubility; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse