Microbial BMAA and the Pathway for Parkinson’s Disease Neurodegeneration

The neurotoxin β- N -methylamino-L-alanine (BMAA) is anatural non-proteinogenic diamino acid produced by several species of bothprokaryotic (cyanobacteria) and eukaryotic (diatoms and dinoflagellates)microorganisms. BMAA has been shown to biomagnify through the food chain in someecosystems, accumulating for example in seafood such as shellfish and fish,common dietary sources of BMAA whose ingestion may have possible neuronalconsequences. In addition to its excitotoxic potential, BMAA has been implicatedin protein misfolding and aggregation, inhibition of specific enzymes andneuroinflammation, all hallmark features of neurodegenerative diseases. However,the exact molecular mechanisms of neurotoxicity remain to be elucidated indetail. Although BMAA is commonly detected in its free form, complexBMAA-containing molecules have also been identified such as the paenilamicins,produced by an insect gut bacterial pathogen. On the other hand, production ofBMAA or BMAA-containing molecules by members of the human gut microbiota, forexample by non-photosynthetic cyanobacteria, the Melainabacteria, remains onlyhypothetical. In any case, should BMAA reach the gut it may interact with cellsof the mucosal immune system and neurons of the enteric nervous system (ENS) andpossibly target the mitochondria. Here, we review the available evidence andhint on possible mechanisms by which chronic exposure to dietary sources of thismicrobial neurotoxin may drive protein misfolding and mitochondrial dysfunctionwith concomitant activation of innate immune responses, chronic low-grade gutinflammation, and ultimately the neurodegenerative features observed across thegut-brain axis in Parkinson’s disease (PD).