Freshwater Cyanobacterial Toxins, Cyanopeptides and Neurodegenerative Diseases

Abstract

Cyanobacteria produce a wide range of structurally diverse cyanotoxins and bioactive cyanopeptides in freshwater, marine, and terrestrial ecosystems. The health significance of these metabolites, which include genotoxic- and neurotoxic agents, is confirmed by continued associations between the occurrence of animal and human acute toxic events and, in the long term, by associations between cyanobacteria and neurodegenerative diseases. Major mechanisms related to the neurotoxicity of cyanobacteria compounds include (1) blocking of key proteins and channels; (2) inhibition of essential enzymes in mammalian cells such as protein phosphatases and phosphoprotein phosphatases as well as new molecular targets such as toll-like receptors 4 and 8. One of the widely discussed implicated mechanisms includes a misincorporation of cyanobacterial non-proteogenic amino acids. Recent research provides evidence that non-proteinogenic amino acid BMAA produced by cyanobacteria have multiple effects on translation process and bypasses the proof-reading ability of the aminoacyl-tRNA-synthetase. Aberrant proteins generated by non-canonical translation may be a factor in neuronal death and neurodegeneration. We hypothesize that the production of cyanopeptides and non-canonical amino acids is a more general mechanism, leading to mistranslation, affecting protein homeostasis, and targeting mitochondria in eukaryotic cells. It can be evolutionarily ancient and initially developed to control phytoplankton communities during algal blooms. Outcompeting gut symbiotic microorganisms may lead to dysbiosis, increased gut permeability, a shift in blood-brain-barrier functionality, and eventually, mitochondrial dysfunction in high-energy demanding neurons. A better understanding of the interaction between cyanopeptides metabolism and the nervous system will be crucial to target or to prevent neurodegenerative diseases.

A Survey of Recently Discovered Naturally Occurring Organohalogen Compounds

“…These Gram-negative bacteria date back 3.6 billion years, and toxic cyanobacterial blooms seem to be increasing, perhaps as a consequence of climate change and waterbody eutrophication . The role of freshwater cyanobacterial toxins on neurodegenerative diseases is reviewed …”

Cyanotoxin Occurrence and Diversity in 98 Cyanobacterial Blooms from Swedish Lakes and the Baltic Sea

“…For humans, the illness associated with the exposure to cyanotoxins is manifested by headaches and nausea with vomiting and diarrhea [14]. Some of cyanotoxins cause liver damage and are tumor-promoters [15,16] while others are neurotoxins that have a paralytic effect [17][18][19]. A toxin-producing cyanobloom becomes thus an extensive societal issue when it hits the surface water reservoirs that are used for the production of drinking water.…”

Bloomin’ Ridiculous: Climate Change, Water Contamination and Algal Blooms in a Land Down Under

“…Health risks, however, surpass water contact during large blooms. Research increasingly indicates cyanobacteria levels below water management triggers can pose public health risks to those with underlying health conditions and/or chronic exposure, such as those living adjacent to bloom-prone water [24]. For example, nasal swabs from people near blooms, without direct water contact, tested positive [25].…”