CEREBRAL-ISCHEMIA INDUCES ALTERATIONS IN TAN AND UBIQUITIN PROTEINS

Excessive stimulation of glutamate receptors and elevation of intracel lular calcium levels initiate the neurodegenerative process resulting from cerebral ischemia. However, the subsequent cascade of molecular c hanges which are of pathogenic significance is less well understood. B reakdown of the cytoskeleton may be involved in the progression from c ompromise of neuronal viability to irreversible damage. Alteration of the microtubule-associated protein tau, as reflected by increased Alz- 50 immunoreactivity, was induced by permanent focal cerebral ischemia in vivo but only in a proportion of neurones. Alz-50 immunoreactive ne urones did not exhibit the characteristics of irreversible ischemic ce ll damage. Increased immunoreactivity to the stress response protein u biquitin was also induced by ischemia in a proportion of neurones. Bot h proteins are components of neurofibrillary tangles in Alzheimer's di sease. Alterations of the microtubule-associated protein tau may be a feature of the early stages of the ischemia-induced degeneration and t he ubiquitin response may be an attempt by compromised neurones to dea l with the presence of abnormal proteins.