Non-protein amino acids and neurodegeneration: The enemy within

  title={Non-protein amino acids and neurodegeneration: The enemy within},
  author={Kenneth J. Rodgers},
  journal={Experimental Neurology},
  • K. Rodgers
  • Published 1 March 2014
  • Biology
  • Experimental Neurology

Toxic Nonprotein Amino Acids

This chapter discusses plant NPAAs that have a similar chemical structure, size, shape, and charge to protein amino acids and can be mistakenly used in protein synthesis, interfere in biochemical pathways, overstimulate receptors, or chelate metal ions.


Many nonprotein amino acids (NPAAs) are plant secondary metabolites and have a similar chemical structure , size, shape and charge to protein amino acids and can be mistakenly used in protein

Neurotoxic non-proteinogenic amino acid β-N-methylamino-L-alanine and its role in biological systems

Natural sources of non-proteinogenic amino acid BMAA and methods for its detection are discussed in this review, as well as the role of BMAA in metabolism of its producers and possible mechanisms of toxicity of this amino acid in different living organisms.

Book: Toxinology, Plant Toxins

This chapter discusses plant NPAAs that have a similar chemical structure, size, shape and charge to protein amino acids and can be mistakenly used in protein synthesis, interfere in biochemical pathways, over-stimulate receptors or chelate metal ions.

Cell death and mitochondrial dysfunction induced by the dietary non-proteinogenic amino acid l-azetidine-2-carboxylic acid (Aze)

The results show that Aze exposure can lead to deleterious effects on human neuron-like cells and highlight the importance of monitoring human Aze consumption via the food chain.

Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

This review is devoted to provide an overview on different established multienzymatic cascades for the production of non-canonical D- α- and L-α-AAs, supplying neophyte and experienced professionals in this field with different illustrative examples in the literature.

Microbial BMAA and the Pathway for Parkinson’s Disease Neurodegeneration

The available evidence is reviewed and hint on possible mechanisms by which chronic exposure to dietary sources of this microbial neurotoxin may drive protein misfolding and mitochondrial dysfunction with concomitant activation of innate immune responses, chronic low-grade gut inflammation, and ultimately the neurodegenerative features observed across the gut-brain axis in Parkinson’s disease (PD).

Non-Proteinogenic Amino Acid β-N-Methylamino-L-Alanine (BMAA): Bioactivity and Ecological Significance

A hypothesis is suggested that this toxic diaminoacid can be used by phytoplankton organisms as a possible allelopathic tool for controlling the population of cyanobacterial cells during a period of intense competition for nitrogen and other resources in various ecosystems.

Cyanobacterial Neurotoxins: Their Occurrence and Mechanisms of Toxicity

The evidence linking β-methylamino-L-alanine (BMAA), a non-protein amino acid, to an unusual neurological disease complex reported on the island of Guam in the 1950s is discussed, and how 60 years later, the role that BMAA plays in human disease is still unclear.

Incorporation of the Non-Proteinaceous Amino Acid β-Methyl-Amino-Alanine Affects Amyloid β Fibril Properties and Toxicity.

It is hypothesize that BMAA was indeed incorporated into Aβ40 molecules and study the structural and dynamical consequences of such misincorporation along with the effect such mutated A β40 peptides have on neuronal cells.



Nonprotein amino acids of plants: significance in medicine, nutrition, and agriculture.

  • E. Bell
  • Biology
    Journal of agricultural and food chemistry
  • 2003
The need to learn more of the nutritive value of nontoxic nonprotein amino acids and to explore the potential of others either as drugs or as leads to drugs in human and veterinary medicine is emphasized.

Toxicity of Non-protein Amino Acids to Humans and Domestic Animals

Non-protein amino acids are common in plants and are present in widely consumed animal feeds and human foods such as alfalfa (Medicago sativa), which contains canavanine, and lentil (Lens culinaris),

Misincorporation of amino acid analogues into proteins by biosynthesis.

The impact of specific oxidized amino acids on protein turnover in J774 cells.

It is shown that incorporation of o- and m-tyrosine resulted in increased protein catabolism, whereas dopa incorporation generated proteins that were inefficiently degraded by cells, and protection against the generation of dopa and other species that promote resistance to proteolysis might prove to be critical in preventing toxicity from oxidative stress in pathologies associated with protein deposition.

The Non-Protein Amino Acid BMAA Is Misincorporated into Human Proteins in Place of l-Serine Causing Protein Misfolding and Aggregation

It is reported that a non-protein amino acid, β-N-methylamino-L-alanine (BMAA), can be misincorporated in place of l-serine into human proteins and this misincorporation can be inhibited by l-Serine.

Biologic Effects of and Clinical Disorders Caused by Nonprotein Amino Acids

Non-protein amino acids take on significance because their misincorporation into proteins can trigger vigorous autoimmune attacks and to what extent this mechanism is responsible for highly prevalent diseases of autoimmunity remains to be determined.

Beyond Guam: The cyanobacteria/BMAA hypothesis of the cause of ALS and other neurodegenerative diseases

  • W. BradleyD. Mash
  • Biology
    Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases
  • 2009
It is hypothesized that individuals who develop neurodegenerations may have a genetic susceptibility because of inability to prevent BMAA accumulation in brain proteins and that the particular pattern of neurodegenersation that develops depends on the polygenic background of the individual.

Cerebral uptake and protein incorporation of cyanobacterial toxin &bgr;-N-methylamino-L-alanine

The time-dependent association of [14C]-L-BMAA in the protein-bound fraction suggests that BMAA may be trapped in new proteins by protein synthesis-dependent processes.

The physiological effect of ingested β-N-methylamino-L-alanine on a glutamatergic synapse in an in vivo preparation.

Discovery and partial characterization of primate motor-system toxins.

BOAA and BMAA are the first members of the excitotoxin family to have been shown to possess chronic motor-system toxic potential and provide a rational basis for searching for comparable endogenous neurotoxins in sporadic and inherited forms of human motor neuron disease.