AIMS: Recent studies have shown that fused-in-sarcoma (FUS) protein is a component of 'neuronal' intranuclear inclusion bodies (INIBs) in the brains of patients with intranuclear inclusion body disease (INIBD). However, the extent and frequency of FUS-immunoreactive structures in INIBD are uncertain. METHODS: We immunohistochemically examined the brain, spinal cord and peripheral ganglia from five patients with INIBD and five control subjects, using anti-FUS antibodies. RESULTS: In controls, the nuclei of both neurones and glial cells were intensely immunolabelled with anti-FUS and neuronal cytoplasm was weakly positive for FUS. In INIBD, neuronal and glial INIBs in the brain and spinal cord were positive for FUS. FUS-positive INIBs were also found in the peripheral ganglia. The proportion of FUS-positive neuronal INIBs relative to the total number of inclusion-bearing neurones ranged from 55.6% to 83.3% (average 73.2%) and that of FUS-positive glial INIBs ranged from 45.9% to 85.7% (average 62.7%). The nucleus and cytoplasm of inclusion-bearing neurones and glial cells showed no FUS immunoreactivity. CONCLUSIONS: These findings suggest that FUS is incorporated into INIBs in both neurones and glial cells and that loss of normal FUS immunoreactivity may result from reduced protein expression and/or sequestration within inclusions.
AIMS: Recent studies have shown that fused-in-sarcoma (FUS) protein is a component of 'neuronal' intranuclear inclusion bodies (INIBs) in the brains of patients with intranuclear inclusion body disease (INIBD). However, the extent and frequency of FUS-immunoreactive structures in INIBD are uncertain. METHODS: We immunohistochemically examined the brain, spinal cord and peripheral ganglia from five patients with INIBD and five control subjects, using anti-FUS antibodies. RESULTS: In controls, the nuclei of both neurones and glial cells were intensely immunolabelled with anti-FUS and neuronal cytoplasm was weakly positive for FUS. In INIBD, neuronal and glial INIBs in the brain and spinal cord were positive for FUS. FUS-positive INIBs were also found in the peripheral ganglia. The proportion of FUS-positive neuronal INIBs relative to the total number of inclusion-bearing neurones ranged from 55.6% to 83.3% (average 73.2%) and that of FUS-positive glial INIBs ranged from 45.9% to 85.7% (average 62.7%). The nucleus and cytoplasm of inclusion-bearing neurones and glial cells showed no FUS immunoreactivity. CONCLUSIONS: These findings suggest that FUS is incorporated into INIBs in both neurones and glial cells and that loss of normal FUS immunoreactivity may result from reduced protein expression and/or sequestration within inclusions.
Authors: Michael Schoen; Jochen M Reichel; Maria Demestre; Stefan Putz; Dhruva Deshpande; Christian Proepper; Stefan Liebau; Michael J Schmeisser; Albert C Ludolph; Jens Michaelis; Tobias M Boeckers Journal: Front Cell Neurosci Date: 2016-01-12 Impact factor: 5.505