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Biochem Pharmacol. 2014 Apr 15;88(4):573-83. doi: 10.1016/j.bcp.2013.11.022. Epub 2013 Dec 19.

Common defects of mitochondria and iron in neurodegeneration and diabetes (MIND): a paradigm worth exploring.

Author information

1
Neuroscience Graduate Program, University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
2
Department of Neurology, University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: rswerdlow@kumc.edu.
3
Neuroscience Graduate Program, University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Clinical Laboratory Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: hzhu@kumc.edu.

Abstract

A popular, if not centric, approach to the study of an event is to first consider that of the simplest cause. When dissecting the underlying mechanisms governing idiopathic diseases, this generally takes the form of an ab initio genetic approach. To date, this genetic 'smoking gun' has remained elusive in diabetes mellitus and for many affected by neurodegenerative diseases. With no single gene, or even subset of genes, conclusively causative in all cases, other approaches to the etiology and treatment of these diseases seem reasonable, including the correlation of a systems' predisposed sensitivity to particular influence. In the cases of diabetes mellitus and neurodegenerative diseases, overlapping themes of mitochondrial influence or dysfunction and iron dyshomeostasis are apparent and relatively consistent. This mini-review discusses the influence of mitochondrial function and iron homeostasis on diabetes mellitus and neurodegenerative disease, namely Alzheimer's disease. Also discussed is the incidence of diabetes accompanied by neuropathy and neurodegeneration along with neurodegenerative disorders prone to development of diabetes. Mouse models containing multiple facets of this overlap are also described alongside current molecular trends attributed to both diseases. As a way of approaching the idiopathic and complex nature of these diseases we are proposing the consideration of a MIND (mitochondria, iron, neurodegeneration, and diabetes) paradigm in which systemic metabolic influence, iron homeostasis, and respective genetic backgrounds play a central role in the development of disease.

KEYWORDS:

Alzheimer's disease; Diabetes; Iron; Mitochondria; Neurodegeneration

PMID:
24361914
PMCID:
PMC3972369
DOI:
10.1016/j.bcp.2013.11.022
[Indexed for MEDLINE]
Free PMC Article

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