Brain. 2012 Feb 17. [Epub ahead of print]
Aviles-Olmos I, Limousin P, Lees A, Foltynie T.
Abstract
Multiple
avenues of research including epidemiology, molecular genetics and cell
biology have identified links between Parkinson's disease and type 2
diabetes mellitus. Several recent discoveries have highlighted common
cellular pathways that potentially relate neurodegenerative processes
with abnormal mitochondrial function and abnormal glucose metabolism.
This includes converging evidence identifying that peroxisome
proliferator activated receptor gamma coactivator 1-α, a key regulator
of enzymes involved in mitochondrial respiration and insulin
resistance, is potentially pivotal in the pathogenesis of
neurodegeneration in Parkinson's disease. This evidence supports
further study of these pathways, most importantly to identify
neuroprotective agents for Parkinson's disease, and/or establish more
effective prevention or treatment for type 2 diabetes mellitus. In
parallel with these advances, there are already randomized trials
evaluating several established treatments for insulin resistance
(pioglitazone and exenatide) as possible disease modifying drugs in
Parkinson's disease, with only preliminary insights regarding their
mechanisms of action in neurodegeneration, which may be effective in
both disease processes through an action on mitochondrial function.
Furthermore, parallels are also emerging between these same pathways
and neurodegeneration associated with Alzheimer's disease and
Huntington's disease. Our aim is to highlight this converging evidence
and stimulate further hypothesis-testing studies specifically with
reference to the potential development of novel neuroprotective agents
in Parkinson's disease.
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