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Is Parkinson's disease a progressive siderosis of substantia nigra resulting in iron and melanin induced neurodegeneration?
Author(s) -
Youdim M.B.H.,
BenShachar D.,
Riederer P.
Publication year - 1989
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.1989.tb01782.x
Subject(s) - substantia nigra , melanin , chemistry , neurodegeneration , lipid peroxidation , oxidative stress , dopamine , autoxidation , oxidative phosphorylation , neuromelanin , biochemistry , fenton reaction , biophysics , microbiology and biotechnology , endocrinology , medicine , dopaminergic , biology , radical , disease
– Razor sharp and high iron deposits are present in the substantia nigra (SN). Although the function of such high iron content is not known, the homeostatis of brain iron is important for normal brain function. The participation of free tissue iron in oxidative stress (OS), resulting in the formation of cytotoxic hydroxyl radical (·OH) from H 2 O 2 (Fenton reaction) and promotion of membrane lipid peroxides by ·OH can no longer be questioned as a biological phenomenon. The highly selective increase of Fe 2+ and Fe 3+ and lipid peroxidation observed in parkinsonian SN points to OS in such brains. Lipid peroxidation proceeds with either Fe 2+ or Fe 3+ provided a mechanism exists to facilitate the interconversion of iron between its redox states. Indeed H 2 O 2 derived from MAO B reaction and autooxidation of dopamine to melanin in the SN can drive the iron dependent Fenton reaction. Furthermore, interaction of iron with melanin may be even more important considering that melanin avidly binds Fe 3+ and reduce it to Fe 2+ , resulting in ·OH generation. Thus, without evoking environmental neurotoxins, the excessive accumulation of free iron in the SN and “melanintrap'’could be the trigger for accelerated cell death and Parkinsonism.