TY - JOUR
T1 - TDP-43 in neurodegenerative disorders
AU - Cook, Casey
AU - Zhang, Yong Jie
AU - Xu, Ya Fei
AU - Dickson, Dennis W.
AU - Petrucelli, Leonard
N1 - Funding Information:
This work was supported by the Mayo Clinic Foundation and funding by NIA R01-AG-026251-01.
PY - 2008/7
Y1 - 2008/7
N2 - 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.
AB - 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.
KW - Amyotropic lateral sclerosis
KW - Frontotemporal dementia
KW - Progranulin
KW - TAR DNA binding protein-43 (TDP-43)
KW - Valosin-containing protein
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U2 - 10.1517/14712598.8.7.969
DO - 10.1517/14712598.8.7.969
M3 - Review article
C2 - 18549326
AN - SCOPUS:47549085411
SN - 1471-2598
VL - 8
SP - 969
EP - 978
JO - Expert Opinion on Biological Therapy
JF - Expert Opinion on Biological Therapy
IS - 7
ER -