Apoptosis May Have Important Contributions To Neurodegenerative Disorders In Humans

It has been discovered that the degeneration of neurons in ALS is a form of apoptosis (Fig. 7). Vulnerable brain and spinal cord regions in ALS (Table I) have abnormalities in the balance of Bcl-2, Bax, and Bak proteins and abnormalities in their interactions (Table IV). However, the initial molecular pathology and upstream signals for motor neurons to engage PCD mechanisms are not known, although we suspect DNA damage. Furthermore, it is still unknown whether the neuronal degeneration in other age-related neurological disorders such as AD, Parkinson's disease, and Huntington's disease is related causally to an abnormal activation of PCD pathways in selectively vulnerable neurons.

Much uncertainty also centers around the possible role of apoptosis in the nerve cell degeneration resulting from cerebral ischemia caused by heart failure, asphyxiation, and stroke. Historically, cellular degeneration resulting from these abnormalities has been considered a form of cellular necrosis, but it has been suggested that postischemic neurodegeneration is apoptosis possibly mediated by a PCD mechanism. However, the contribution of apoptosis to the selective degeneration of neurons after ischemia is not yet resolved.

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