| Popis: |
Changes in Ca homeostasis in non-neuronal cells have been found both in aging and in Alzheimer’s disease (1). Similar changes have also been described in the brain, including hippocampal neurons (2–5). A comprehensive review of Ca changes in aging cells and during Alzheimer’s disease has been published (6). Dysregulation of free Ca in the cytosol may induce changes in Ca-dependent proteolytic systems in the cell. Calpains (EC 3.4.22.17) are Ca-activated, neutral cysteine proteases found in all cells. Two types of calpains have been identified: μ-calpain and m-calpain, requiring micro- and millimolar concentrations of Ca, respectively for, in vitro, initiation of activity (7,8). A specific inhibitory protein, calpas-tatin, is also part of this highly regulated proteolytic system. Two lines of evidence suggest that calpains have a regulatory rather than a degradative function in the cell. First, Ca is a well established regulator of many coordinated cellular functions. Second, calpains appear to cleave substrates only to a limited extent, preferentially between rather than within the domains of the substrate proteins (8). Limited proteolysis by calpains may be an important regulatory mechanism mediating biological responses elicited by extracellular stimuli. In an earlier study on post mortem brain material (9) we obtained evidence for an increased calpain activity in the brain during an active stage of Alzheimers disease characterized by a high amount of neuropathological changes. We have also obtained evidence for an increased proteolytic activity and a decreased calpastatin activity in erythrocytes from patients with Alzheimer’s disease (10). A reduced calpastatin activity in erythrocytes from patients with Alzheimer’s disease has also been observed by Soldati et al. (11). |
