Session Information
Date: Tuesday, June 6, 2017
Session Title: Parkinson's Disease: Pathophysiology
Session Time: 1:45pm-3:15pm
Location: Exhibit Hall C
Objective: To test the hypothesis that brain insulin resistance (i.e. decreased insulin/insulin like growth factor (IGF)-1 signaling) occurs in the substantia nigra pars compacta (SNc) and the putamen, two structures that are strongly involved in the neurodegenerative process in Parkinson’s disease (PD).
Background: PD is a progressive neurodegenerative disorder characterized by the accumulation of alpha-synuclein in neurons forming Lewy bodies. Studies point to a potential involvement of abnormal insulin/IGF-1 signalling in the pathogenesis of PD as serum and cerebrospinal fluid levels of IGF-1 in PD patients are increased. Moreover, a small open-label phase 2 clinical trial assessing the effects of the glucagon-like peptide-1 (GLP-1) agonist exenatide, a well-tolerated FDA-approved antidiabetic drug that facilitates insulin/IGF-1 signalling, has reported beneficial effects on motor symptoms and cognition in PD patients. A follow up study showed persisting positive effects one year after the end of the study.
Methods: Insulin resistance was assessed by measuring protein expression levels of insulin receptor substrate-1 phosphorylated on serine 312 and serine 616 (IRS-1pS312/S616) in postmortem brain samples of PD patients and brains of AAV-SYN rat, a PD rodent model based on the overexpression of A53T mutated human alpha-synuclein (h-α-synA53T) by using adeno-associated viral vectors. The extent of dopamine loss in AAV-SYN rats was documented by stereological quantification of tyrosine hydroxylase (TH) positive neurons in the SNc.
Results: We here show increased IRS-1pS312 expression levels in PD patients and AAV-SYN rats. Specifically, neurons of the putamen and surviving TH positive neurons of the SNc in PD patients and its animal model counterpart showed increased IRS-1pS312 expression.
Conclusions: Our results suggest that insulin resistance plays a role in the pathogenesis of PD. They further provide the rationale for pursuing the clinical development of GLP-1 analogues for treating PD.
To cite this abstract in AMA style:
F. Bassil, M.-H. Canron, N. Dutheil, A. Vital, E. Bezard, P.-O. Fernagut, W. Meissner. Brain insulin resistance in Parkinson’s disease [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/brain-insulin-resistance-in-parkinsons-disease/. Accessed May 16, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/brain-insulin-resistance-in-parkinsons-disease/