Specific metal-catalysed protein oxidation reactions in chronic degenerative disorders of ageing: focus on Alzheimer's disease and age-related cataracts.
Abnormalities of protein aggregation and deposition may play an important role in the pathophysiology of a diverse set of chronically progressive degenerative disorders including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease and age-related cataracts. We propose that aberrant metalloprotein reactions may be a common denominator in these diseases. In these instances, an abnormal reaction between a protein and redox active metal ions (especially copper or iron) promotes the generation of reactive oxygen species, and possibly, protein radicalization. These products then lead to chemical modification of the protein, alterations in protein structure and solubility, and oxidative damage to surrounding tissue. In this review, we explore these ideas by focusing on two common diseases of ageing, Alzheimer's disease and age-related cataracts. Understanding the metalloprotein biochemistry in both diseases may lead to a better understanding of the underlying pathophysiology in both disorders and suggest novel targets for therapeutic agents.
Bush
A I
AI
Laboratory for Oxidation Biology, Genetics and Aging Unit, Massachusetts General Hospital, Boston, MA 02129, USA.
Goldstein
L E
LE
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D002386:Cataract / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D002908:Chronic Disease; D006801:Humans; D008667:Metalloproteins / Q000378:metabolism* / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000503:physiopathology / Q000628:therapy; D010084:Oxidation-Reduction
D008667:Metalloproteins