Publikationsdatum:
2006-10-07
Beschreibung:
Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neumann, Manuela -- Sampathu, Deepak M -- Kwong, Linda K -- Truax, Adam C -- Micsenyi, Matthew C -- Chou, Thomas T -- Bruce, Jennifer -- Schuck, Theresa -- Grossman, Murray -- Clark, Christopher M -- McCluskey, Leo F -- Miller, Bruce L -- Masliah, Eliezer -- Mackenzie, Ian R -- Feldman, Howard -- Feiden, Wolfgang -- Kretzschmar, Hans A -- Trojanowski, John Q -- Lee, Virginia M-Y -- AG10124/AG/NIA NIH HHS/ -- AG17586/AG/NIA NIH HHS/ -- T32 AG00255/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2006 Oct 6;314(5796):130-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17023659" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Amino Acid Sequence
;
Amyotrophic Lateral Sclerosis/*metabolism/pathology
;
Antibodies, Monoclonal
;
*Brain Chemistry
;
Cerebral Cortex/chemistry/pathology
;
DNA-Binding Proteins/*analysis/chemistry/genetics/immunology
;
Dementia/genetics/*metabolism/pathology
;
Fluorescent Antibody Technique
;
Hippocampus/chemistry/pathology
;
Humans
;
Immunoblotting
;
Molecular Sequence Data
;
Motor Neurons/chemistry/pathology
;
Neurons/chemistry/pathology
;
Peptide Fragments/chemistry
;
Phosphorylation
;
Spinal Cord/*chemistry/pathology
;
Ubiquitin/*analysis
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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