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Cellular oxidant/antioxidant balance has become the subject of intense study, particularly focused on brain aging and neurodegenerative disorders. There is now evidence to suggest that reduction of cellular expression and activity of antioxidant proteins and the resulting increase of oxidative stress are fundamental causes for both the aging processes and neurodegenerative diseases. However, to survive different types of injuries, brain cells have evolved networks of different responses, which detect and control diverse forms of stress. Efficient functioning of maintenance and repair process seems to be crucial for both survival and physical quality of life. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of several genes termed ˵vitagenes.″ Among these, heat-shock proteins (Hsps), proteasome, and mitochondrial uncoupling protein systems are highly conserved mechanisms responsible for the preservation and repair of the correct conformation of cellular macromolecules, such as proteins, RNA, and DNA. Recent studies have shown that the heat-shock response contributes to establishing a cytoprotective state in a wide variety of human diseases, including ischemia and reperfusion damage, inflammation, metabolic disorders, cancer, infection, trauma, and aging. Among the various Hsps, Hsp32 also known as heme oxygenase I (HO-1), has received considerable attention, as it has been recently demonstrated that HO-1 induction, by generating the vasoactive molecule carbon monoxide (CO) and the potent antioxidant bilirubin, could represent a protective system potentially active against brain oxidative injury. The major neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Friedreich's ataxia (FA), are all associated with the presence of abnormal proteins. Given the broad cytoprotective properties of the heat-shock response, there is now strong interest in discovering and developing pharmacological agents capable of inducing the heat-shock response. These findings have opened up new perspectives in medicine and pharmacology, as molecules inducing this defense mechanism appear to be possible candidates for novel cytoprotective strategies. Particularly, modulation of endogenous cellular defense mechanisms such as the heat-shock response, and the proteasomal system, through nutritional antioxidants or pharmacological compounds may represent an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration. Moreover, by maintaining or recovering the activity of vitagenes, it would be possible to delay the aging process and decrease the occurrence of age-related diseases with resulting prolongation of a healthy life span. [ABSTRACT FROM AUTHOR]