Potential Role of Heterocyclic Aromatic Amines in Neurodegeneration

Abstract

Heterocyclic aromatic amines (HAAs) are mainly formed in the pyrolysis process during high-temperature cooking of meat. Meat consumption is very typical of the western diet, and the amount of meat consumption in the eastern countries is growing rapidly; HAAs represents widespread exposure. HAAs are classified as possible human carcinogens; numerous epidemiological studies have demonstrated regular consumption of meat with HAAs as risk factor for cancers. Specific HAAs have received major attention. For example, 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine has been extensively studied as a genotoxicant and mutagen, with emergent literature on neurotoxicity. Harmane has been extensively studied for a role in essential tremors and potentially Parkinson's disease (PD). Harmane levels have been demonstrated to be elevated in blood and brain in essential tremor patients. Meat consumption has been implicated in the etiology of neurodegenerative diseases; however, the role of toxicants formed during meat preparation has not been studied. Epidemiological studies are currently examining the association between HAAs and risk of neurodegenerative diseases such as essential tremors and PD. Studies from our laboratory and others have provided strong evidence that HAA exposure produces PD and Alzheimer's disease-relevant neurotoxicity in cellular and animal models. In this review, we summarize and critically evaluate previous studies on HAA-induced neurotoxicity and the molecular basis of potential neurotoxic effects of HAAs. The available studies provide strong support for the premise that HAAs may impact neurological function and that addressing gaps in understanding of adverse neurological outcomes is critical to determine whether these compounds are modifiable risk factors.

Heterocyclic aromatic amines (HAAs) target mitochondrial physiology

“…HAAs are produced in meat upon high temperature cooking, through Maillard reaction between amino acids, sugar, and creatinine or pyrolysis of aromatic amino acids (11,12). HAAs have been classified into different subclasses, α-carbolines, aminoimidazoaazarenes (AIAs), and β-carbolines (9). Amongst AIA HAAs 2-Amino-1methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) is the most abundant and extensively studied HAA (13), where levels in chicken may reach 480 ng/g and human exposures of 0.5 -1 µg/day (though exposures could be as high as 5-50 µg) (14)(15)(16)(17).…”

“…The study of dietary neurotoxicants is important to a) determine the underlying pathogenic mechanisms that may influence neurodegeneration and b) identify modifiable risk factors that can limit the onset or progression of disease pathology. Previous studies have identified significant neurotoxic effects of dietary toxicants such as heterocyclic aromatic amines (HAA) on dopaminergic and cholinergic neurons, linking their potential association with AD and PD (5)(6)(7)(8)(9)(10). HAAs are produced in meat upon high temperature cooking, through Maillard reaction between amino acids, sugar, and creatinine or pyrolysis of aromatic amino acids (11,12).…”

Sex-specific transcriptional rewiring in the brain of Alzheimer’s disease patients

“…Several of these chemicals have been linked to neurodegeneration. For instance, heterocyclic aromatic amines formed during high-temperature cooking of meats, including PhIP, have been linked to Parkinson’s and Alzheimer’s diseases ( Syeda and Cannon, 2022 ). Exposure to cupric oxide promoted neurotoxicity and neurodegeneration in a Caenorhabditis elegans model ( Mashock et al, 2016 ).…”

Heterocyclic Aromatic Amines and Risk of Kidney Stones: A Cross-Sectional Study in US Adults

“…Heterocyclic aromatic amines are a class of polycyclic aromatic compounds that are formed naturally during the heating of protein-based foods such as meat (19). The average exposure to meat HAAs varies by the nation due to differences in the diets of the East and West, especially the amount of meat consumed (20). Studies have shown that the average daily exposure to HAAs is 565.3 ng/d in Americans, 69.4 ng/d in Europeans, and 49.94 ng/d in the Chinese population (21)(22)(23).…”