Cysteamine Gliopathy in situ: A Cellular Stress Model for the Biogenesis of Astrocytic Inclusions

  title={Cysteamine Gliopathy in situ: A Cellular Stress Model for the Biogenesis of Astrocytic Inclusions},
  author={Hyman M. Schipper and Marc B. Mydlarski and X Wang},
  journal={Journal of Neuropathology and Experimental Neurology},
In cultured astroglia, cysteamine induces the accumulation of peroxidase-positive cytoplasmic inclusions in the context of a generalized cellular stress response. In the present study, systemic cysteamine administration over a 3 week period induced HSP27, 72, 90, and GRP94 (stress proteins) in astrocytes and significantly increased numbers of peroxidase-positive astrocytic inclusions in the various brain regions relative to controls. Similar patterns of HSP expression were also observed at 24… 
A Cellular Stress Model for the Differential Expression of Glial Lysosomal Cathepsins in the Aging Nervous System
It is demonstrated that cysteamine suppresses cathepsin B mRNA levels and immunoreactive protein in cultured astroglia, whereas cat hepsin D mRNA and protein levels are significantly augmented by CSH exposure in these cells.
Cysteamine Pretreatment of the Astroglial Substratum (Mitochondrial Iron Sequestration) Enhances PC12 Cell Vulnerability to Oxidative Injury
The aging-associated accumulation of redox-active iron in subcortical astrocytes may facilitate the bioactivation of dopamine to neuronotoxic free radical intermediates and thereby predispose the senescent nervous system to PD and other neurodegenerative disorders.
Experimental induction of corpora amylacea‐like inclusions in rat astroglia
Long‐term exposure of neonatal rat astrocyte cultures to CSH resulted in the formation of large spherical, PAS‐positive cytoplasmic inclusions which are highly reminiscent of, if not identical to, human CA.
A Cellular Stress Model for the Sequestration of Redox‐Active Glial Iron in the Aging and Degenerating Nervous System
The results of this study suggest that stress‐related trapping of nonheme iron by astroglial mitochondria may be an important mechanism underlying the pathological accumulation of redox‐active iron in the basal ganglia of subjects with Parkinson's disease.
Astrocyte Mitochondria: A Substrate for Iron Deposition in the Aging Rat Substantia Nigra
Histochemical, ultrastructural, and elemental microanalytical techniques were used to demonstrate the existence of peroxidase-positive astroglia in the substantia nigra of adult rats, and mitochondrial sequestration of redox-active iron in aging nigral astrogalia may be one factor predisposing the senescent nervous system to parkinsonism and other neurodegenerative disorders.
Iron: Oxidative Stress and Neurodegeneration
CSH attenuates de novo porphyrin-heme biosynthesis in astroglia but may induce punctate orange-red autofluorescence in the cytoplasm of these cells by promoting large numbers of damaged, porphirin-containing mitochondria to form tight aggregates within the nascent gliosomes.
Role of Porphyrin Sequestration in the Biogenesis of Iron-Laden Astrocytic Inclusions in Primary Culture
Astrocytes in subcortical regions of the mammalian brain progressively accumulate iron-rich, autofluorecent cytoplasmic inclusions as a function of aging. Cysteamine (CSH) accelerates the appearance