Objective: To evaluate the glycolytic energy homeostasis in Parkinson’s disease (PD), and to define the effects of PD pharmacotherapies on glycolytic dynamics
Background: Neuronal energy supply is highly dependent to hexokinase (HK-1) to ATP production. L-DOPA/D1agonist/GLP-1R analog induce HK-2 transcription via Akt kinase to higher energy demand (catabolism), A2AR antagonist-Istradefylline (IST) induce AMPK-lysosome to activate autophagy with energy conservation (anabolism)(Figure 1).
Method: (Methods)The cohort recruited 185 PD and 20 de novo PD patients (age, 66±11; female/male, 113/92; duration, 9.8±7; modified H&Y (on) 3.0±1.0, (off) 4.0±0.9; LEDD 729±255). The metabolic effects of the L-DOPA/IST combination therapy were prospectively measured for six years from 2013 to 2019. The newly developed dyskinesia and body weight changes (⊿loss or ⊿gain) were evaluated. Biological marker; serum HK-2 (Colorimetric enzyme activity assay; ab136957), insulin-like growth factor type 1 (IGF-1) (immune-radiometric assay; Daiichi, Japan) were measured.
(Research ethics) This study was approved by the ethics committee of our hospital, and consent was obtained from the patients.
Results: De novo PD patients (L-DOPA naïve) revealed lower serum HK-II activity compared to controls (p<0.01). Overall prevalence of newly developed dyskinesia was 17.1 %, loss of weight (⊿loss) was 56.8%, and depression 6.3 %, those comorbidity were correlated with lower circulatory HKII and IGF-1 bioactivity (p<0.01). The prevalence of insulin resistance was frequent; 19.4%, but impulse control and related disorders (ICD-RD) was low; 2% .
Conclusion: We first showed the blood HKII levels related with dyskinesia and metabolic disorders. The pharmacological effects of L-DOPA/IST combination therapy were tolerable as glycolytic metabolic conservation.
References: 1) Naomi Kanzato, et al. Parkinson’s disease therapy with Istradefylline and biomarker of epigenetics. J Neurology and Neuroscience 2020, in press.
To cite this abstract in AMA style:
N. Kanzato, K. Nakachi, S. Mochizuki,. Blood hexokinase reduction in de novo Parkinson’s disease and remodeling of glycolytic energy homeostasis with L-DOPA/Istradefylline combination therapy [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/blood-hexokinase-reduction-in-de-novo-parkinsons-disease-and-remodeling-of-glycolytic-energy-homeostasis-with-l-dopa-istradefylline-combination-therapy/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/blood-hexokinase-reduction-in-de-novo-parkinsons-disease-and-remodeling-of-glycolytic-energy-homeostasis-with-l-dopa-istradefylline-combination-therapy/