ADVANCED GLYCATION END-PRODUCTS IN NEURODEGENERATION - MORE THAN EARLY MARKERS OF OXIDATIVE STRESS

Oxidative stress is believed to play a decisive role in the pathogenes is of Parkinson's disease (PD). In addition, Lewy bodies, densely cros slinked intracellular protein deposits formed from cytoskeletal compon ents, accumulate in presymptomatic stages of the disease. Recent findi ngs indicate that ''advanced glycation end products'' (AGEs) are the m ajor structural crosslinkers that cause the transformation of soluble neurofilament proteins to insoluble Lewy bodies. AGE formation is incr eased under conditions of oxidative stress, such as early GSH depletio n, that are evident in the substantia nigra of PD patients, and is inh ibited by radical scavengers and thiol antioxidants. Because AGEs not only are markers of oxidative stress but are also active participants in cell signaling by activation of glial cells to produce superoxide a nd nitric oxide, they can be considered part of a vicious cycle, which finally leads to neuronal cell death in the substantia nigra in PD.