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Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by pure neurofibrillary tau pathology involving mainly basal ganglia and brain stem nuclei. One of the kinases involved in tau phosphorylation is glycogen synthase 3 kinase (GSK3). In mammals GSK3 is present in two isoforms, alpha and beta regulated by phosphorylation: phosphorylation of Ser9 in GSK3beta or Ser21 in GSK3alpha leads to inactivation while phosphorylation of Tyr216 in GSK3beta or Tyr279 in GSK3alpha leads to activation. We analyzed the protein levels of GSK3alpha/beta and of the phosphorylated forms GSK3beta S(9), GSK3beta Y(216), GSK3alpha Y(279) in brain tissues of subjects with PSP. The analysis failed to show significant differences of all GSK3 isoforms in PSP in comparison to age-matched control cases. This negative result argues against the role of GSK3 in the pathogenesis of PSP.

Growth factors are major signaling agents regulating neuron-glia dialogue. Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin growth factor-I (IGF-I) and insulin (INS) induce neuronal and astroglial cell proliferation and differentiation. This is true also for estrogens that influence astrocytes and exert neuroprotectant activity. In this study interactions between growth factors and estradiol on DNA labeling and glial fibrillary acidic protein (GFAP) and vimentin expression in cultured astrocytes were investigated. DNA labeling was significantly stimulated by bFGF pretreatment followed by 24 h estradiol and EGF or IGF-I or INS added in the last 12 h. Western blotting showed also a modulation of GFAP and vimentin expression in treated astrocytes. This suggests the occurrence of a crucial growth factor-estradiol interaction on DNA labeling and cytoskeletal protein expression during astrocyte proliferation and differentiation in culture.

T lymphocytes control the extent of the immune reaction by recognizing the antigen in connection with class II histocompatibility surface molecules, coded by genes located on the HLA-D locus. The expression of HLA-DR antigens is confined to a few antigen presenting cells, like lymphocytes and macrophages, which can therefore induce the initial phase of the immune reaction. We report that also Schwann cells (SC) from patients with Charcot-Marie-Tooth disease (CMT), an hereditary disorder of the peripheral nervous system, are able to express HLA-DR antigens. Human SC cultures were carried out from sural nerve biopsies of CMT and normal control cases. Cultures were tested on day 7, 14, 21 and 28, with double immunofluorescence technique using rabbit antiserum anti-S-100 and mouse anti-HLA-DR monoclonal antibody. SC from CMT were HLA-DR positive since the first few days, continuing to express class II antigens for all the duration of the culture. The presence of class II antigens on cultured SC from CMT disease suggests that immune-mediated mechanisms may be relevant in the pathogenesis of this degenerative disorder of the peripheral nervous system.