Freshwater Cyanobacterial Toxins, Cyanopeptides and Neurodegenerative Diseases

Galina Nugumanova, Eugene D. Ponomarev, Sholpan Askarova, Elizaveta Fasler-Kan, Natasha S. Barteneva

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Article number233
JournalToxins
Volume15
Issue number3
DOIs
Publication statusPublished - Mar 2023

Keywords

  • Alzheimer’s disease
  • amyotrophic lateral sclerosis
  • BMAA
  • cyanopeptides
  • cyanotoxins
  • gut-brain axis
  • harmful algal blooms
  • microcystin
  • mistranslation
  • neurodegenerative disease
  • non-proteogenic amino acids
  • Parkinson’s disease

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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