Neurodegenerative diseases pathologic mechanisms

Copper is essential for some of the enzymes that have a role in brain metabolism. Sophisticated mechanisms balance copper import and export to ensure proper nutrient levels (homeostasis) while minimizing toxic effects. Several neurodegenerative diseases including AD are characterized by modified copper homeostasis. This change seems to contribute either directly or indirectly to increased oxidative stress, an important factor in neuronal toxicity. The association of misfolded proteins and modified copper homeostasis appears to be important in the pathological progression of AD [Donnelly et al., 2007],... 

The pathological characteristic of Parkinson s disease is the selective degeneration of dopamine neurons in the pars compacta of the substantia nigra. The mechanism for the loss of neurons remains to be elucidated, and recently apoptosis has been proposed as a death process in Parkinson s disease. For example, the level of a product of the oxidative stress, 4-hydroxy-2-nonenal protein adduct, was found to increase in the nigral neurons of parkinsonian brains. Peroxynitrite (see Figure 13.6) has been proposed to be involved in the neuronal cell death in some neurodegenerative diseases, such as amyotrophic lateral sclerosis. 

Depressive symptoms often accompany neurodegenerative disorders, especially in PD and HD. Although the monoamine hypothesis of depression has long been proposed, the pathologies and mechanisms for depressive disorders remain only partially understood. A number of proposed mechanisms for depression such as diminishing neurotrophic factors and neuroinflammation appear to be similar to those implicated in neurodegenerative diseases [330, 331]. Many patients suffering from these disorders are treated with conventional antidepressants. 

Due to the unique properties of its nervous system, C. elegans has been well studied for establishing models of human neurodegenerative diseases (like Parkinson s disease, PD) and revealing the pathological mechanisms of these diseases [57-60]. Neurotoxins 6-hydroxydopamine (6-OHDA), l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine... 

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