OVEREXPRESSION AND ABNORMAL MODIFICATION OF THE STRESS PROTEINS ALPHA-B-CRYSTALLIN AND HSP27 IN ALEXANDER-DISEASE

Alexander disease is a leukodystrophy characterized by the presence of numerous Rosenthal fibers, inclusion bodies in astrocytes. A major co mponent of Rosenthal fibers is alphaB-crystallin, some of which is ubi quitinated. In this report, we show that Alexander central nervous sys tem (CNS) tissues contain elevated messenger P-NA and protein levels o f both alphaB-crystallin and the related small beat shock protein, hsp 27, and that Rosenthal fibers contain hsp27. The alphaB-crystallin and hsp27 polypeptide isoform patterns of Alexander disease CNS are also distinct from those of control samples, suggesting that postranslation al modifications may be involved in Rosenthal fiber formation. We adva nce the hypothesis that Rosenthal fibers may be regarded as stress pro tein inclusions formed in astrocytes as part of a chronic stress respo nse to an as yet unknown stimulus in the CNS of Alexander patients.