Astroglia and Protein Aggregation Diseases

Many neurodegenerative disorders like Alzheimer’s, Parkinson’s, prion and polyglutamine diseases are caused by gain-of-function mechanisms in which the disease-causing protein accumulates in the form of insoluble protein aggregates or inclusion bodies [1,2]. Whether these aggregated proteins directly cause neurodegeneration is still controversial; however, it is widely believed that soluble form of the proteins and/or micro-aggregates are more toxic than the larger inclusions. Spinocerebellar ataxia 1 (SCA1) is one such protein aggregation disease, characterized by loss of motor coordination due to the degeneration of cerebellar Purkinje cells (PCs) and brain stem neurons [3]. In SCA1, the expanded mutant ataxin-1 protein aggregates into nuclear inclusions (NIs) [4]. However, before the appearance of NIs, SCA1 PCs exhibit cytoplasmic vacuoles rich in astroglial derived S100B protein, which is exclusively expressed in Bergmann glia (BG) of the cerebellum [5]. These S100B containing cytoplasmic vacuoles appear as early as 16 days postnatally in PCs of the asymptomatic SCA1 transgenic (Tg) mice. No S100B vacuoles were seen in wildtype animals and A02 Tg line with normal CAG repeats [5].