A metabolic profile of polyamines in parkinson disease: A promising biomarker

  • Ann Neurol. 2019 Aug;86(2):251-263. doi: 10.1002/ana.25516.
Shinji Saiki  1 ,  Yukiko Sasazawa  1  2 ,  Motoki Fujimaki  1 ,  Koji Kamagata  3 ,  Naoko Kaga  4 ,  Hikari Taka  4 ,  Yuanzhe Li  1 ,  Sanae Souma  1 ,  Taku Hatano  1 ,  Yoko Imamichi  1 ,  Norihiko Furuya  1  5 ,  Akio Mori  1 ,  Yutaka Oji  1 ,  Shin-Ichi Ueno  1 ,  Shuko Nojiri  6 ,  Yoshiki Miura  4 ,  Takashi Ueno  4 ,  Manabu Funayama  1  2  7 ,  Shigeki Aoki  3 ,  Nobutaka Hattori  1  2  5  7
Affiliations
  • 1. Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 2. Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 3. Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 4. Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 5. Division for Development of Autophagy Modulating Drugs, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 6. Clinical Research Center, Juntendo University, Tokyo, Japan.
  • 7. Laboratory of Genomic Medicine, Center for Genomic and Regenerative Medicine, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
PMID: 31155745 DOI: 10.1002/ana.25516
Abstract

Objective: Aging is the highest risk factor for Parkinson disease (PD). Under physiological conditions, spermidine and spermine experimentally enhance longevity via Autophagy induction. Accordingly, we evaluated the ability of each polyamine metabolite to act as an age-related, diagnostic, and severity-associated PD biomarker.

Methods: Comprehensive metabolome analysis of plasma was performed in Cohort A (controls, n = 45; PD, n = 145), followed by analysis of 7 polyamine metabolites in Cohort B (controls, n = 49; PD, n = 186; progressive supranuclear palsy, n = 19; Alzheimer disease, n = 23). Furthermore, 20 patients with PD who were successively examined within Cohort B were studied using diffusion tensor imaging (DTI). Association of each polyamine metabolite with disease severity was assessed according to Hoehn and Yahr stage (H&Y) and Unified Parkinson's Disease Rating Scale motor section (UPDRS-III). Additionally, the Autophagy induction ability of each polyamine metabolite was examined in vitro in various cell lines.

Results: In Cohort A, N8-acetylspermidine and N-acetylputrescine levels were significantly and mildly elevated in PD, respectively. In Cohort B, spermine levels and spermine/spermidine ratio were significantly reduced in PD, concomitant with hyperacetylation. Furthermore, N1,N8-diacetylspermidine levels had the highest diagnostic value, and correlated with H&Y, UPDRS-III, and axonal degeneration quantified by DTI. The spermine/spermidine ratio in controls declined with age, but was consistently suppressed in PD. Among polyamine metabolites, spermine was the strongest Autophagy Inducer, especially in SH-SY5Y cells. No significant genetic variations in 5 genes encoding Enzymes associated with spermine/spermidine metabolism were detected compared with controls.

Interpretation: Spermine synthesis and N1,N8-diacetylspermidine may respectively be useful diagnostic and severity-associated biomarkers for PD. ANN NEUROL 2019;86:251-263.

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