An Overview of Endogenous Catechol-Isoquinolines and Their Related Enzymes: Possible Biomarkers for Parkinson’s Disease

Abstract

For the most common neurodegenerative disorders, there is no simple, obvious, and effective biomarker for disease identification. Plasma biomarkers of neurodegenerative disorders should play an important role in early detection and diagnosis of diseases. The catechol isoquinoline compounds are considered as possible neurotoxins involved in the pathogenesis of Parkinson's disease (PD). These catechol isoquinolines and enzymes involved in their biosynthesis and metabolism may be endogenous factors in the pathogenesis of PD. As we know, there exists a salsolinol N-methyltransferase (SNMT) in human brain and lymphocyte. In normal postmortem human brain regions, frontal cortex, caudate, putamen, and thalamus, the SNMT activity was significantly higher than the control, and was well relevant to PD. In parkinsonian lymphocytes, the SNMT activity was much higher than in control patients. In addition, there was significant positive correlation between the SNMT activity in the lymphocyte and the level of Nmethylsalsolinol in cerebrospinal fluid from the same untreated PD patients. Mass spectrometry-based biomarker discovery, undoubtedly, is still in its early stage of infancy. However, in light of the potential of this technology to provide deep coverage of the body fluid proteomes, it will certainly consolidate its role in development molecular medicine into clinical practice.

Catechol Tetrahydroisoquinolines Enhance a-Synuclein Aggregation and Specify the Neurotoxicity to Dopaminergic Neurons

“…CTIQs together with their nitrogen methylation and oxidation products are the structure analogs of MPTP and MPP + . So we have known that these CTIQs are the products of DA that would be a reasonable explanation for the specific degeneration of dopaminergic neurons in PD patients [10]. Also, there is a chiral c enantiomer in the C1 location of CTIQ, which is the reason of existence of (R) and (S)-enantiomer of CTIQ.…”

“…Unlike exogenous neurotoxins, CTIQs is a group of products which could be synthesized in the brain of human based on the condensation of DA and some certain aldehydes. So it is proposed that they might be the key factors involved in α-syn aggregation [10][11][12] In this review, we will describe the relationship between CTIQs and the abnormal aggregation of α-syn and try to provide a helpful insight into therapeutic approaches for PD.…”

Non-enzymatic molecular damage as a prototypic driver of aging

“…In some cases, the members are confined to different tissues or compartments; however, they often also occur in the same place and are thus doomed to react. That is how cytotoxic Pictet-Spengler products can be formed from biogenic amines and aldehydes (16,17). The same is true for 5-S-cysteinyl dopamine, which is formed in the brain from dopamine-derived quinones via nucleophilic thiol addition (18) ( Fig.…”

“…A likely explanation of this discrepancy may be the observation that the negative feedback regulation of steroidogenic tissues is mediated by central catecholaminergic neurons, whose functions become compromised with aging (79). Catecholamines and their metabolites and parametabolites are prone to Pictet-Spenglertype interactions yielding products implicated in age-associated parkinsonism (17), and are subject to oxidation yielding neurotoxins (80), including quinones (81). These quinones in turn polymerize ( Fig.…”

The epigenetic mechanisms involved in mitochondrial dysfunction: Implication for Parkinson’s disease

“…Exogenous neurotoxins possess a slightly lower risk in PD development due to a lower population exposure rate. The exogenous neurotoxins include MPTP, pesticides, heavy metals, and solvents, wildly employed to develop animal models of PD to explore the pathological mechanisms of PD ( 54 , 55 ). Environmental neurotoxins cause similar PD clinical manifestations that share common pathways of mitochondrial dysfunction ( 47 ).…”