TDP-43 functions and pathogenic mechanisms implicated in TDP-43 proteinopathies

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منابع مشابه

Molecular Neuropathology of TDP-43 Proteinopathies

The identification of TDP-43 as the major component of the pathologic inclusions in most forms of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS) resolved a long-standing enigma concerning the nature of the ubiquitinated disease protein under these conditions. Anti-TDP-43 immunohistochemistry and the rec...

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Drosophila Answers to TDP-43 Proteinopathies

Initially implicated in the pathogenesis of CFTR and HIV-1 transcription, nuclear factor TDP-43 was subsequently found to be involved in the origin and development of several neurodegenerative diseases. In 2006, in fact, it was reported for the first time the cytoplasmic accumulation of TDP-43 in ubiquitin-positive inclusions of ALS and FTLD patients, suggesting the presence of a shared underly...

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Expression of TDP-43 C-terminal Fragments in Vitro Recapitulates Pathological Features of TDP-43 Proteinopathies.

The disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS) was identified recently as the TDP-43 (TAR DNA-binding protein 43), thereby providing a molecular link between these two disorders. In FTLD-U and ALS, TDP-43 is redistributed from its normal nuclear localization to form cytoplasmic insoluble aggregates. Mo...

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Clinical and pathological continuum of multisystem TDP-43 proteinopathies.

OBJECTIVE To determine the extent of transactivation response DNA-binding protein with a molecular weight of 43 kDa (TDP-43) pathology in the central nervous system of patients with clinically and autopsy-confirmed diagnoses of frontotemporal lobar degeneration with and without motor neuron disease and amyotrophic lateral sclerosis with and without cognitive impairment. DESIGN Performance of ...

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Glia as primary drivers of neuropathology in TDP-43 proteinopathies.

A long-standing mystery has been understanding why neurons die in devastating neurodegenerative disorders, such as Alzheimer’s disease, Parkinson disease, and amyotrophic lateral sclerosis (ALS). Abnormal intracellular protein aggregates are a hallmark feature of many neurodegenerative conditions. Based on this fundamental observation, numerous studies have attempted to shed light on the causal...

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ژورنال

عنوان ژورنال: Trends in Molecular Medicine

سال: 2011

ISSN: 1471-4914

DOI: 10.1016/j.molmed.2011.06.004