Alpha B-crystallin is a major component of glial cytoplasmic inclusions in multiple system atrophy

• Published in: Neurotoxicity research 2005, Vol.7 (1-2), p.77-85
• Main Authors: Pountney, D L, Treweek, T M, Chataway, T, Huang, Y, Chegini, F, Blumbergs, P C, Raftery, M J, Gai, W P
• Format: Article
• Language: English
• Subjects: alpha-Crystallin B Chain - biosynthesis; alpha-Crystallin B Chain - genetics; Amino Acid Sequence; Animals; Humans; Inclusion Bodies - genetics; Inclusion Bodies - metabolism; Inclusion Bodies - pathology; Molecular Sequence Data; Multiple System Atrophy - metabolism; Multiple System Atrophy - pathology; Neuroglia - metabolism; Neuroglia - pathology; Rats; Tumor Cells, Cultured
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/BF03033778

Multiple system atrophy (MSA) is characterized by the formation of oligodendroglial cytoplasmic inclusions (GCIs) consisting of alpha-synuclein filaments. AlphaB-crystallin, a small chaperone protein that binds to unfolded proteins and inhibits aggregation, has been documented in GCIs. We investigated the relative abundance and speciation of alphaB-crystallin in GCIs in MSA brains. We also examined the influence of alphaB-crystallin on the formation of cytoplasmic inclusions in cultured glial cells. Immunohistochemistry and confocal microscopy revealed alphaB-crystallin is a prominent component of GCIs, more abundant than in Lewy bodies in Lewy body dementia. One- and two-dimensional gel electrophoresis and mass spectrometric analysis of GCIs immunopurified from MSA brains indicated that alphaB-crystallin is a major protein component with multiple post-translationally modified species. In cultured C6 glioma cells treated with the proteasomal inhibitor, lactacystin, to induce accumulation of ubiquitinated proteins, a subset of cells showed increased cytoplasmic staining for alphaB-crystallin. Proteasome-inhibited cells transfected with GFP-tagged alpha-synuclein resulted in ubiquitin- and alphaB-crystallin-positive aggregates resembling GCIs in MSA brains. Our results indicate that alphaB-crystallin is a major chaperone in MSA, and suggest a role of the protein in the formation of inclusion bodies in glial cells.