Cytoplasmic inclusions of TDP-43 in neurodegenerative diseases:: A potential role for caspases

• Autores: Troy T. Rohn
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 24, Nº. 8, 2009, págs. 1081-1086
• Idioma: inglés
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• Resumen

  • TAR DNA-binding protein-43 (TDP-43) proteinopathies are classified based upon the extent of modified TDP-43 inclusions and include a growing number of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin immunoreactive, tau negative inclusions (FTLD-U) and FTLD with motor neuron disease (FTLD-MND). In addition, TDP-43 inclusions have also been identified in a number of other neurodegenerative disorders including Alzheimer�s disease, corticobasal degeneration, Lewy body related diseases and Pick�s disease. Current understanding suggests that in these diseases, TDP-43 is relocated from the nucleus to the cytoplasm and sequestered into inclusions that contain modified TDP-43. Major modifications of TDP-43 have been identified as being hyperphosphorylation and proteolytic cleavage by caspases. In this review a summary of the major findings regarding the proteolytic modification of TDP-43 will be discussed as well as potential toxic-gain mechanisms these fragments may cause including cytoskeletal disruptions.