Proteases In Β-Amyloid Metabolism: Potential Therapeutic Targets Against Alzheimer‘;S Disease
Proteases are extremely important signaling molecules that are involved in numerous vital processes. Protease signaling pathways are strictly regulated, and therefore the dysregulation of their activity can lead to pathologies such as cardiovascular and inflammatory diseases, cancer, and neurological disorders. An illustration of the functional role of proteases in physiological processes is demonstrated in the metabolism of β-amyloid. Under normal physiological conditions, the steady-state level of β-amyloid peptide in the brain is determined by the rate of production from amyloid precursor protein via β- and γ-secretases and rate of degradation by the activity of several known metallopeptidases. In conditions that affect the activity of these proteases (for example, genetic mutations, environmental factors, or age), overactive secretases or underactive β-amyloid-degrading enzymes could shift the balance of amyloid metabolism toward abnormal β-amyloid deposition in the brain, an early and invariant feature of all forms of Alzheimer's disease (AD). These proteases thus represent potential therapeutic targets against AD, and consequently, regulation of their activity by drugs is now considered as an important strategy in the neuroprotection.
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