Introduction

Many of the key proteins which are involved in brain function, for example neurotransmitter synthesis, involve metalloenzymes, notably iron and copper. An obvious example is the Fe2+ enzyme, tyrosine hydroxylase which synthesizes dihydroxyphenylalanine (DOPA) from tyrosine (Figure 1), for dopamine formation. Despite this need for iron, it has become increasingly clear that a small elevation in brain iron concentration will cause a great number of disorders of the central nervous system, which are often age-related, since iron progressively accumulates in brain with age.

However, iron is a Damocles sword [1], since, in addition to being catalyti-cally essential for many enzymes, it can also catalyze the formation of reactive oxygen and nitrogen species (ROS and RNS), resulting in oxidative stress, which

Tyrosine tyrosine hydroxylase

Tetrahydrobiopterin + O2

Dihydrobiopterin + H2O

Dihydrobiopterin + H2O

Dihydroxyphenylalanine (l-DOPA)

Figure 1. The synthesis of l-DOPA from tyrosine by tyrosine hydroxylase. l-DOPA is then transformed into adrenaline, and also into the skin pigment, melanin. (Reproduced with permission from [169]).

Dihydroxyphenylalanine (l-DOPA)

Figure 1. The synthesis of l-DOPA from tyrosine by tyrosine hydroxylase. l-DOPA is then transformed into adrenaline, and also into the skin pigment, melanin. (Reproduced with permission from [169]).

can cause neurodegeneration. Two classes of iron-related neurodegenerative disorders can be distinguished; the first due to iron accumulation in specific brain regions, and the second resulting from defective iron metabolism and perturbation of iron homeostasis [2]. As life expectancy increases and, as a consequence, brain iron accumulates, we would expect the occurrence of iron-related neurodegenerative diseases to inexorably increase [3].

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