Abstract
Catabolic insufficiency in humans leads to the gradual accumulation of a number of pathogenic compounds associated with age-related diseases, including atherosclerosis, Alzheimer's disease, and macular degeneration. Removal of these compounds is a widely researched therapeutic option, but the use of antibodies and endogenous human enzymes has failed to produce effective treatments, and may pose risks to cellular homeostasis. Another alternative is "medical bioremediation," the use of microbial enzymes to augment missing catabolic functions. The microbial genetic diversity in most natural environments provides a resource that can be mined for enzymes capable of degrading just about any energy-rich organic compound. This review discusses targets for biodegradation, the identification of candidate microbial enzymes, and enzyme-delivery methods.
Highlights
The continuous renewal of biological components is essential for the proper functioning and survival of mammalian cells
We provided a number of examples in which the abnormal accumulation of biological "waste" leads to pathological conditions; this situation is further exacerbated by the inefficiencies of cell function found with increasing age
Since the idea of medical bioremediation was first conceived several years ago [4,5], technical barriers have been overcome, and knowledge has developed that further substantiates its potential feasibility
Summary
The continuous renewal of biological components is essential for the proper functioning and survival of mammalian cells. High levels of 27OH-7KC still accumulate in lesions and foam cells This may indicate that expression of sterol 27hydroxylase alone is not sufficient to overcome atherosclerotic progression or that the enzyme is not expressed highly enough to compensate for the increased cholesterol and oxysterol burden. We provided a number of examples in which the abnormal accumulation of biological "waste" leads to pathological conditions; this situation is further exacerbated by the inefficiencies of cell function found with increasing age Observations that these accumulations are often slow and progress over the course of a lifetime indicate that the targeted degradation of these deleterious compounds could have enormous therapeutic value if performed before advanced pathology surfaces. Due to the age-related nature of the aggregates, it seems unlikely that continuous treatments will be required, where an adaptive immune response would be a major complication
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