Accumulation of TDP-43 and alpha-actin in an amyotrophic lateral sclerosis patient with the K17I ANG mutation

作者:Seilhean Danielle*; Cazeneuve Cecile; Thuries Valerie; Russaouen Odile; Millecamps Stephanie; Salachas Francois; Meininger Vincent; LeGuern Eric; Duyckaerts Charles
来源:Acta Neuropathologica, 2009, 118(4): 561-573.
DOI:10.1007/s00401-009-0545-9

摘要

A K17I mutation in the ANG gene encoding angiogenin has been identified in a case that we previously published as ALS with neuronal intranuclear protein inclusions (Seilhean et al. in Acta Neuropathol 108:81-87, 2004). These inclusions were immunoreactive for smooth muscle alpha-actin but not for angiogenin. Moreover, they were not labeled by anti-TDP-43 antibodies, while numerous cytoplasmic inclusions immunoreactive for ubiquitin, p62 and TDP-43 were detected in both oligodendrocytes and neurons in various regions of the central nervous system. In addition, expression of smooth muscle alpha-actin was increased in the liver where severe steatosis was observed. This is the first neuropathological description of a case with an ANG mutation. Angiogenin is known to interact with actin. Like other proteins involved in ALS pathogenesis, such as senataxin, TDP-43 and FUS/TLS, it plays a role in RNA maturation.

  • 出版日期2009-10