Journal Article (Review Article)

DZNE-2020-03203

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetics and iron in the systems biology of Parkinson's disease and some related disorders.

Funke, C. ; Schneider, S. A. ; Berg, D. (Corresponding author)DZNE* ; Kell, D. B.

2013
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.neuint.2012.11.015

Abstract: The systems biology approach to complex diseases recognises that a potentially large number of biochemical network elements may be involved in disease progression, especially where positive feedback loops can be identified. Most of these network elements will be encoded by genes, for which different alleles may affect the network(s) differentially. A primary requirement is therefore to determine the relevant gene-network relationships. A corollary of this is that identification of the network should thereby allow one to 'explain' or account for any genetic associations. We apply this approach to Parkinson's disease, a disease characterised by apoptotic death of neurons of the substantia nigra, and coupled significantly to a derangement of iron metabolism. We thereby account for the involvement of various genes and biochemical pathways associated with Parkinsonism, including seemingly unconnected ones involving iron, α-synuclein, parkin, mitochondrial respiration and biology, ceramide production, lysosome biology, Lewy body formation, and so on. Although such an analysis necessarily recognises that there is no unitary 'cause' of Parkinson's, it also recognises that each of the elements contributing can or does effectively converge on a particular mode of apoptotic cell death in dopaminergic neurons, often involving iron-mediated hydroxyl radical formation. Overall, the systems biology approach allows us to propose at least one coherent synthesis of the rather disparate literature surrounding the aetiology of Parkinson's disease, and thereby to suggest some (synergistic) targets for ameliorating the disease and its progression.

Keyword(s): Biocatalysis (MeSH) ; Brain: metabolism (MeSH) ; Cell Death (MeSH) ; Humans (MeSH) ; Iron: metabolism (MeSH) ; Organelles: metabolism (MeSH) ; Parkinson Disease: genetics (MeSH) ; Parkinson Disease: metabolism (MeSH) ; Parkinson Disease: pathology (MeSH) ; Systems Biology (MeSH) ; Iron

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Contributing Institute(s):

1. Parkinson's Disease Genetics (AG Berg ; AG Berg)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2013

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