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2017 ; 26
(9
): 1560-1571
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gab.com Text
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A New Treatment Strategy for Parkinson s Disease through the Gut-Brain Axis: The
Glucagon-Like Peptide-1 Receptor Pathway
#MMPMID29113464
Kim DS
; Choi HI
; Wang Y
; Luo Y
; Hoffer BJ
; Greig NH
Cell Transplant
2017[Sep]; 26
(9
): 1560-1571
PMID29113464
show ga
Molecular communications in the gut-brain axis, between the central nervous
system and the gastrointestinal tract, are critical for maintaining healthy brain
function, particularly in aging. Epidemiological analyses indicate type 2
diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders
including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging
shows a major correlative association. Common pathophysiological features exist
between T2DM, AD, and PD, including oxidative stress, inflammation, insulin
resistance, abnormal protein processing, and cognitive decline, and suggest that
effective drugs for T2DM that positively impact the gut-brain axis could provide
an effective treatment option for neurodegenerative diseases. Glucagon-like
peptide-1 (GLP-1)-based antidiabetic drugs have drawn particular attention as an
effectual new strategy to not only regulate blood glucose but also decrease body
weight by reducing appetite, which implies that GLP-1 could affect the gut-brain
axis in normal and pathological conditions. The neurotrophic and neuroprotective
effects of GLP-1 receptor (R) stimulation have been characterized in numerous in
vitro and in vivo preclinical studies using GLP-1R agonists and dipeptidyl
peptidase-4 inhibitors. Recently, the first open label clinical study of
exenatide, a long-acting GLP-1 agonist, in the treatment of PD showed
long-lasting improvements in motor and cognitive function. Several double-blind
clinical trials of GLP-1R agonists including exenatide in PD and other
neurodegenerative diseases are already underway or are about to be initiated.
Herein, we review the physiological role of the GLP-1R pathway in the gut-brain
axis and the therapeutic strategy of GLP-1R stimulation for the treatment of
neurodegenerative diseases focused on PD, for which age is the major risk factor.