Iron and other metals in the pathogenesis of Parkinson's disease: Toxic effects and possible detoxification

Journal of Inorganic Biochemistry
Geir BjørklundJan Aaseth

Abstract

Of the documented cases of Parkinson's disease (PD), about 10% have a genetic background. The remaining cases of PD have unknown etiology. Thus, environmental factors appear to play a pathogenic role in most of the PD cases. Several of the so far known PD inducing chemicals appear to increase the formation of mitochondrial reactive oxygen species (ROS). A suspected environmental factor is the non-proteinogenic amino acid β-methylamino-l-alanine (BMAA), which may act to carry iron species into the brain and disrupt correct biosynthesis of proteins. In addition, in epidemiological studies, it has been reported a connection between PD and metal exposures, including iron, mercury, manganese, and lead. Research has shown elevated iron levels in the substantia nigra of PD patients. Mitochondrial dysfunction induced by genetic or environmental factors appears to evoke cascades of biochemical events, which include non-physiological leakage of ROS and arrest of the sensitive production of dopamine. A combination of increased ROS and loosely chelated iron causes neurotransmitter dysfunction. Recent research indicates that treatment with exogenous chelators, such as deferiprone, apomorphine, and hinokitiol, can inhibit PD progression. The...Continue Reading

Citations

Sep 27, 2019·CNS Drugs·Niels BergslandRobert Zivadinov
Nov 23, 2019·Molecular Neurobiology·Geir BjørklundJan Aaseth
Sep 4, 2020·Experimental Biology and Medicine·Santosh R D'Mello, Mark C Kindy

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