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

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

Identification and Validation of N-Acetylputrescine in Combination With Non-Canonical Clinical Features As a Parkinson’s Disease Biomarker Panel

“…In a small scale clinical study (n=33), putrescine and N1-Acetylspermidine in cerebrospinal fluid (CSF) were significantly higher in PD patients compared to the control group [15]. Furthermore, the plasma level of N8-acetylspermidine and N1, N8-diacetylspermidine demonstrated significant accuracy in ROC curve analysis and positively correlated with H&Y stages [30].…”

“…Due to the possible influence of other comorbidities within these groups, the use of acyl carnitines became a challenge for diagnosis. Moreover, increasing evidence suggests the possible role of polyamines in PD underlined several potential PD biomarkers in the mechanism of polyamine synthesis and metabolism [15,30]. In a small scale clinical study (n=33), putrescine and N1-Acetylspermidine in cerebrospinal fluid (CSF) were significantly higher in PD patients compared to the control group [15].…”

Dietary Mitophagy Enhancer: A Strategy for Healthy Brain Aging?

“…Spermidine is a polyamine which exists in all living cells, including microorganism, plants, and animals [ 32 ]. There are three different sources for spermidine in humans: endogenous biosynthesis, exogenous food intake, and microbial activity in the intestines [ 33 , 34 ]. Additional supplementation of polyamine precursors, such as ornithine and related amino acids, is supposed to enhance polyamine synthesis [ 35 ].…”

Chromogenic Chemodosimeter Based on Capped Silica Particles to Detect Spermine and Spermidine

“…In fact, the total Spd + Spm concentration in the blood is lower in 60–80-year-old individuals than in 31–56-year-old individuals [ 16 ]. For this reason, these polyamines have been considered promising biomarkers for the early detection of aging related illnesses, such as Parkinson’s disease [ 17 ]. Therefore, spermidine seems to play an important role in memory and longevity [ 18 ].…”