Accumulation of TDP-43 and alpha-actin in an amyotrophic lateral sclerosis patient with the K17I ANG mutation.
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.
Seilhean
Danielle
D
Département de Neuropathologie, UPMC Université Paris 06, AP-HP, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, INSERM UMR-S 546 (DS) and UMR-S 679 (CD), 47-83 boulevard de l'Hôpital, Paris cedex 13, France. danielle.seilhean@psl.aphp.fr
Cazeneuve
Cécile
C
Thuriès
Valérie
V
Russaouen
Odile
O
Millecamps
Stéphanie
S
Salachas
François
F
Meininger
Vincent
V
Leguern
Eric
E
Duyckaerts
Charles
C
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000150:complications; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology; D012259:Ribonuclease, Pancreatic / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
D000199:Actins; D004268:DNA-Binding Proteins; C046366:angiogenin; D012259:Ribonuclease, Pancreatic