harman and Parkinson-Disease

Harman and norharman, two neuroactive β-carbolines, are present in several plants and in thermally processed foods. They exhibited a wide spectrum of biological and pharmacological effects, including antioxidant, neuroprotective, and anti-inflammatory effects. In this article, we review the progress of recent research on the presence of these compounds in food, as well as their various biological and neuroactive properties. Our findings strongly suggest that some foods, especially coffee, can act as a rich source of β-carbolines, which may possibly be associated with a reduced risk for serious neurodegenerative diseases, such as Parkinson's and Alzheimer's.

Topics: Animals; Brain; Brain Chemistry; Carbolines; Essential Tremor; Food; Food Handling; Harmine; Humans; Neurodegenerative Diseases; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Plant Extracts

Parkinson's disease (PD) is a late-life neurodegenerative disease. Genetic and environmental factors play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin that shows structural resemblance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).. In 2002 and 2007, we demonstrated elevated blood harmane concentrations [HA] in essential tremor (ET) cases. We now assessed whether blood [HA] were elevated in Parkinson's disease (PD) as well.. Blood [HA] were quantified by high performance liquid chromatography. Subjects comprised 113 PD cases and 101 controls.. Mean log blood [HA] in PD cases was double that of controls (0.59±0.63 g(-10)/ml vs. 0.27±0.63 g(-10)/ml, p<0.001). A non-parametric test on non-transformed data (median blood [HA]=3.31 g(-10)/ml in cases and 1.44 g(-10)/ml in controls) also showed this difference (p<0.001). In unadjusted and then adjusted logistic regression analyses, log blood [HA] was associated with PD (odds ratio [OR]unadjusted 2.31, 95% confidence interval [CI] 1.46-3.67, p<0.001; OR(adjusted) 2.54, 95% CI 1.55-4.16, p<0.001). In PD, log blood [HA] co-varied with family history, being lowest in PD cases with no family history (0.54±0.60 g(-10)/ml) and highest in PD cases with a family history of both ET and PD (0.84±0.68 g(-10)/ml) (p=0.06).. Blood harmane appears to be elevated in PD. The finding needs to be reproduced in additional cohorts to assess its generalizability. The higher concentration in familial PD suggests that the mechanism may involve genetic factors.

Topics: Aged; Female; Harmine; Humans; Male; Neurotoxins; Parkinson Disease; Risk Factors

Death of dopaminergic neurons in Parkinson's disease (PD) may partially be caused by synthesis and accumulation of endogenous and exogenous toxins. Because of structural similarity to MPTP, beta-carbolines, like norharman and harman, have been proposed as putative neurotoxins. In vivo they may easily be formed by cyclization of indoleamines with e.g. aldehydes. For further elucidation of the role of beta-carbolines in neurodegenerative disorders harman and norharman levels in cerebrospinal fluid (CSF) were measured in 14 patients with PD and compared to an age- and sex-matched control group (n = 14). CSF levels of norharman and harman in PD were significantly higher compared to controls. These results may suggest a possible role of harman and norharman or its N-methylated carbolinium ions in the pathophysiological processes initiating PD. However the origin of increased levels of these beta-carbolines remains unclear. On the one hand one may speculate, that unknown metabolic processes induce the increased synthesis of harman and norharman in PD. On the other hand a possible impact of exogenous sources may also be possible.

Topics: Adult; Aged; Carbolines; Case-Control Studies; Female; Harmine; Humans; Male; Middle Aged; Neurotoxins; Parkinson Disease

Several lines of evidence suggest that endogenous and exogenous toxins may play a major role in the pathogenesis of Parkinson's disease (PD). In the brain aromatic beta-carbolines, like harman or norharman, may be formed by cyclization of indoleamines. Because of the structural similarity to MPTP, beta-carbolines have been proposed as endogenous toxins. For further elucidation of the role of beta-carbolines in neurodegenerative disorders, harman and norharman plasma levels were measured in 36 patients with PD and compared to an age- and sex-matched control group. Plasma levels of norharman in PD were significantly higher compared to the control group. Harman in the plasma of Parkinsonian patients was also elevated compared to the controls, but this difference was not significant. On the one hand these results may suggest a possible role of beta-carbolines in the pathophysiological processes initiating PD. But on the other hand one may speculate that elevated levels of norharman and harman are due to an endogenous upregulation, caused by unknown metabolic processes to reduce oxidative stress by inhibiting e.g. monoaminooxidases in neurons.

Topics: Aged; Aged, 80 and over; Carbolines; Case-Control Studies; Female; Harmine; Humans; Male; Middle Aged; Neurotoxins; Parkinson Disease