Focal increases of axoplasmic Ca2+, aggregation of sodium-calcium exchanger, N-type Ca2+ channel, and actin define the sites of spheroids in axons undergoing oxidative stress.

Axonal spheroids occur as part of the pathology of a variety of neurologic diseases. Reactive oxygen species (ROS) trigger formation of spheroids, axonal severing, and Ca(2+) overload. The mechanisms by which ROS lead to the spheroid formation at specific axonal sites remain elusive.

Mitochondrial calcium and its regulation in neurodegeneration induced by oxidative stress.

A proposed mechanism of neuronal death associated with a variety of neurodegenerative diseases is the response of neurons to oxidative stress and consequent cytosolic Ca(2+) overload. One hypothesis is that cytosolic Ca(2+) overload leads to mitochondrial Ca(2+) overload and prolonged opening of the permeability transition pore (PTP), resulting in mitochondrial dysfunction. Elimination of cyclophilin D (CyPD), a key regulator of the PTP, results in neuroprotection in a number of murine models of neurodegeneration in which oxidative stress and high cytosolic Ca(2+) have been implicated.

Activation of the mitochondrial permeability transition pore modulates Ca2+ responses to physiological stimuli in adult neurons.

The participation of mitochondria in cellular and neuronal Ca(2+) homeostatic networks is now well accepted. Yet, critical tests of specific mitochondrial pathways in neuronal Ca(2+) responses have been hampered because the identity of mitochondrial proteins that must be integrated within this dynamic system remain uncertain. One putative pathway for Ca(2+) efflux from mitochondria exists through the formation of the permeability transition pore (PTP) that is often associated with cellular and neuronal death.

Estrogen facilitates neurite extension via apolipoprotein E in cultured adult mouse cortical neurons.

Literature review suggests a close relationship between estrogen and apolipoprotein E (ApoE) in the central nervous system. Epidemiology studies show that estrogen replacement therapy (ERT) decreases the morbidity from several chronic neurological diseases. Alleles of ApoE modify the risk for and progression of the same diseases.