Potential contribution of proteases to neuronal damage.

Calpain was first discovered 30 years ago. Two major isoforms were subsequently isolated and purified. The presence of an endogenous protein inhibitor, calpastatin, was later discovered.

P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease.

Primary rat microglia stimulated with either ATP or 2'- and 3'-O-(4-benzoylbenzoyl)-ATP (BzATP) release copious amounts of superoxide (O(2)(-)*). ATP and BzATP stimulate O(2)(-)* production through purinergic receptors, primarily the P2X(7) receptor. O(2)(-)* is produced through the activation of the NADPH oxidase.

cAMP delays beta-amyloid (25-35) induced cell death in rat cortical neurons.

Beta-amyloid (A beta) accumulation is believed to contribute to neuronal cell death in Alzheimer's disease. To understand the role of cAMP in the regulation of A beta induced cell death, we used 8-chlorophenylthio-cAMP (8-CPT-cAMP, a cAMP analog) to raise intracellular cAMP levels. Exposure of rat cortical neurons to A beta(25-35) resulted in a gradual increase in lactate dehydrogenase (LDH) over 48 h, which was preceded by a transient elevation in caspase-3-like activity.

Light and confocal microscopic studies of evolutionary changes in neurofilament proteins following cortical impact injury in the rat.

Previous studies have shown that traumatic brain injury (TBI) produces progressive degradation of cytoskeletal proteins including neurofilaments (e.g., neurofilament 68 [NF68] and neurofilament 200 [NF200]) within the first 24 h after injury.

Maitotoxin induces calpain but not caspase-3 activation and necrotic cell death in primary septo-hippocampal cultures.

Maitotoxin is a potent toxin that activates voltage and receptor-mediated Ca2+ channels, resulting in Ca2+ overload and rapid cell death. We report that maitotoxin-induced cell death is associated with activation of calpain but not caspase-3 proteases in septo-hippocampal cell cultures. Calpain and caspase-3 activation were examined by accumulation of protease-specific breakdown products to alpha-spectrin.