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Jackob Moskovitz
Oxidative damage
to proteins is considered to be one of the major causes of aging and
age-related diseases, and thus mechanisms have evolved to prevent or
reverse these modifications. Methionine is one of the major targets
of reactive oxygen species (ROS), where it is oxidized to methionine
sulfoxide (MetO). Recently evidence has accumulated suggesting that
methionine oxidation may play an important role in the progression of
neurodegenerative diseases like Alzheimer's and Parkinson's disease.
Oxidative alteration of Met to Met(O) is reversed by the methionine
sulfoxide reductases (MsrA which reduces S-MetO and MsrB which reduces
R-MetO). This may prevent irreversible protein damage and as a consequence
extend the organism's life span. A major biological role of Msrs is
suggested by the fact that the MsrA null mouse (MT) exhibits a neurological
disorder in the form of ataxia ("tip toe walking"), is more
sensitive to oxidative stress, and has a shorter life span (by~40%)
than wild-type (WT) mice. However, a major open question is how these
important antioxidants function, and is the methionine oxidation/reduction
cycle analogous to the cysteine oxidation/reduction or protein-phosphorylation
/ dephosphorylation mechanisms involved in cell signaling. Publications (click
here
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