Sortilin-related receptor CNS expressed 2 (SorCS2) is localized to Bunina bodies in amyotrophic lateral sclerosis

• Amyotrophic lateral sclerosis (ALS) is one of the most devastating neurodegenerative disease.
• ALS-specific Bunina bodies are immunoreactive for SorCS2, a member of vacuolar protein sorting 10 family proteins (VPS10Ps).
• Immunoreativity for VPS10Ps, sortilin and SorLA, is decreased in anterior horn cells of ALS patients.
• VPS10Ps may be involved in the pathomechanisms of ALS.

Sortilin-related receptor CNS expressed 2 (SorCS2) is one of the vacuolar protein sorting 10 family proteins (VPS10Ps) that have pleiotropic roles in protein trafficking and intracellular and intercellular signaling. Bunina bodies (BBs) are specifically detected in the lower motor neurons in patients with amyotrophic lateral sclerosis (ALS). BBs are immunolabeled with antibodies against cystatin C, transferrin and peripherin and are considered to originate from the endoplasmic reticulum, which is part of the protein sorting pathway. The present study investigated whether VPS10Ps are involved in the formation of BBs in ALS. We immunohistochemically examined the spinal cord from patients with ALS and control subjects using antibodies against VPS10Ps (sortilin, SorLA, SorCS1, SorCS2 and SorCS3). In normal controls, antibodies against VPS10Ps immunolabeled the cytoplasm of anterior horn cells in a fine granular pattern. In ALS, almost all BBs (95.1%) were strongly immunopositive for SorCS2, and immunoreativity for sortilin and SorLA was decreased in anterior horn cells. These findings suggest that VPS10Ps may be involved in the disease process of ALS.