DNA, Nuclear Cell Signaling and Neurodegeneration

Abstract

During aging, it is normal for neurodegeneration to occur, sometimes leading to Alzheimer's disease, Parkinson's disease and other conditions. Stroke can cause massive neurodegeneration. There is controversy concerning the causes of these conditions. Lifestyle will be examined as a possible cause of many neurodegenerative conditions in this chapter. It is possible that the blood-brain barrier is the initial site of damage that ultimately leads to inflammation in the brain that may produce some brain diseases. During stroke, thrombosis lodged in arteries leading to ischemia and reperfusion produces cell damage in many brain regions. This chapter will discuss mechanisms of adipokine and toxic lipid induced oxygen radical formation and damage to the blood-brain barrier. Active oxygen species such as hydrogen peroxide cross cell membranes, penetrate into the nucleus and very rapidly damage DNA. DNA peroxidation produces DNA fragments. DNA repair enzymes become activated and rapidly deplete cellular energy reserves, such as NAD and ATP. This drastically alters cell function and viability. Endothelial cell death makes the blood-brain barrier leak and may allow the infiltration of activated inflammatory cells that produce oxygen radicals that damage neurons and other brain cells. Neuronal death occurs through apoptosis and necrosis.