Abstract
The tubulin polymerization-promoting protein (TPPP)/p25alpha was identified as a brain specific protein, is associated with microtubules (MTs) in vitro and can promote abnormal MT assembly. Furthermore it has aggregation promoting properties and is a constituent in pathological protein deposits of neurodegenerative diseases. In the brain, TPPP/p25alpha is present in myelinating oligodendrocytes. Here we show, using cultured rat brain oligodendrocytes, that TPPP/p25alpha expression is increasing during development in culture, and particularly in immature cells is associated with the centrosome. MT binding properties in oligodendrocytes are rather low, however, when MTs are disassembled by nocodazole, TPPP/p25alpha accumulates in the perinuclear region. Treatment of oligodendrocytes with the proteasomal inhibitor MG-132 (1 micaroM; 18 h) caused an increase in the amount of TPPP/p25alpha by about 40%, a decrease in its solubility, and led to the appearance of TPPP/p25alpha-positive cytoplasmic inclusions, which stained with thioflavin S and resembled inclusion bodies. Hence, it might be speculated that acute or chronic malfunction of the proteasomal degradation system, leading to the accumulation of aggregation prone proteins and the pro-aggregatory protein TPPP/p25alpha or to the aggregation of TPPP/p25alpha on its own, is causally related to the protein aggregation process in a variety of neurodegenerative diseases.