Semaglutide is Neuroprotective and Reduces α-Synuclein Levels in the Chronic MPTP Mouse Model of Parkinson’s Disease.

Semaglutide is Neuroprotective and Reduces α-Synuclein Levels in the Chronic MPTP Mouse Model of Parkinson’s Disease.

Publication date: Feb 12, 2019

Parkinson’s disease (PD) is a progressive neurological motor control disorder. A key feature is the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (α-syn). No current treatment is on the market that slows or halts disease progression. Previous studies have shown that glucagon-like peptide-1 (GLP-1) receptor agonists have neuroprotective effects in animal models of PD. In addition, in a phase II clinical trial, the GLP-1 receptor agonist exendin-4 has shown good protective effects in PD patients. In the present study, we have investigated the neuroprotective effects of the GLP-1 analogues semaglutide (25 nmol/kg ip. once every two days for 30 days) and liraglutide (25 nmol/kg ip. once daily for 30 days) in the chronic MPTP mouse model of PD. Both drugs are currently on the market as a treatment for Type II diabetes. Our results show that both semaglutide and liraglutide improved MPTP-induced motor impairments. In addition, both drugs rescued the decrease of tyrosine hydroxylase (TH) levels, reduced the accumulation of α-syn, alleviated the chronic inflammation response in the brain, reduced lipid peroxidation, and inhibited the mitochondrial mitophagy signaling pathway, and furthermore increased expression of the key growth factor GDNF that protects dopaminergic neurons in the substantia nigra (SN) and striatum. Moreover, the long- acting GLP-1 analogue semaglutide was more potent compared with once daily liraglutide in most parameters measured in this study. Our results demonstrate that semaglutide may be a promising treatment for PD. A clinical trial testing semaglutide in PD patients will start shortly.

Concepts Keywords
Agonist Alpha
Brain Neuroprotection
Clinical Trial Parkinson’s disease
Diabetes Substantia nigra
Dopaminergic MPTP
GDNF Incretin
Glucagon Liraglutide
Growth Factor Semaglutide
Inflammation Branches of biology
Lipid Peroxidation Peptide hormones
Liraglutide Organ systems
Midbrain Medical specialties
Mitochondrial Motor control disorder
Motor Control Chronic inflammation
MPTP
Neurological
Neurons
Neuroprotective
Parkinson
Peptide
Progressive
Receptor
Striatum
Substantia Nigra
Tyrosine Hydroxylase

Semantics

Type Source Name
pathway BSID Oxidative Stress
disease MESH oxidative stress
gene UNIPROT GDNF
disease MESH growth
pathway BSID Mitophagy
disease MESH inflammation
drug DRUGBANK L-Tyrosine
drug DRUGBANK Liraglutide
gene UNIPROT GCG
gene UNIPROT ZGLP1
gene UNIPROT GLP1R
drug DRUGBANK Glucagon
disease MESH disease progression
gene UNIPROT SYNM
gene UNIPROT FYN
drug DRUGBANK Semaglutide

Similar

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *