Formation of GFAP cytoplasmic inclusions in astrocytes and their disaggregation by alpha B-crystallin

In several neuropathological conditions, alpha B-crystallin and glial fibri llary acidic protein (GFAP) accumulate and form cytoplasmic inclusions in a strocytes, To explore the pathogenesis of the inclusions and the possible f unctions of the accumulated alpha B-crystallin, GFAP and alpha B-crystallin were overexpressed in cultured astrocytes by transient transfection. Human GFAP formed filamentous, cytoplasmic inclusions in mouse astrocytes, NIH3T 3 cells, rat C6 glioma cells, and human U251 glioma cells. These human GFAP inclusions did not contain the endogenous vimentin or beta-tubulin, and th e intermediate filament and microtubular networks of the transfected cells appeared normal. alpha B-crystallin and hsp25 were associated with the GFAP inclusions. Increasing intracellular alpha B-crystallin levels using recom binant adenoviruses, either before or after GFAP inclusions were formed, de creased the number of inclusion-bearing astrocytes and converted the human GFAP from an inclusion to a spread, filamentous form. These results suggest that alpha B-crystallin reorganizes abnormal intermediate filament aggrega tes into the normal filamentous network.