References

10 Neurotransmitters, Neuroregulators and Neurotoxins in Plants 145
O
OH
O
N
H
NH 2
O
OH
ß-oxalylaminoalanine (BOAA)
H 3C
H
N
NH 2
OH
ß-methylaminoalanine (BMAA)
Fig.10.6. Neurotoxic, non-protein amino acids from plants
O
that can inhibit protein synthesis, disrupt urea cycle function or impair
neurotransmission (Bell 2003). One example of a neurologically damaging
aminoacidfromplantsisβ-oxalylaminoalanine (BOAA) found in Lathyrus
sativus. L. sativus (grasspea or chickling vetch, guaya in Ethiopia, khesari
in India) is a small legume grown and eaten throughout many parts of
the world. Consumption of seeds high in BOAA is thought to be the cause
of lathyrism, a neurodegenerative disease characterized by spastic paraparesis.
Taken in small quantities, pigeonpea is not neurotoxic but during
droughts or when other food is limited, epidemics in lathyrism have occurred
(Spencer, 1999). In 1977 an outbreak of lathyrism in Ethiopia caused
more than 2,500 people to become ill (Spencer and Palmer 2003). Both
BOAA and a related compound BMAA (Fig. 10.6) can damage neurons
but the potency and specificity of these amino acids is quite low (Lindstrom
et al. 1990). The compounds are classified as excitotoxins, a toxic
molecule that overstimulates stimulates neurons resulting in cellular damage
or cell death. In cell cultures, both BOAA and β-methylaminoalanine
(BMAA) injure neurons in a dose-dependent manner and require various
metabolic cofactors such as bicarbonate (Weiss et al. 1989). As a result
of both the general complexity of progressive neurodegenerative diseases
and the mechanisms of action of compounds that are not acutely toxic,
the study of plant-based neurotoxins requires an interdisciplinary team of
neurologists, chemists and botanists. One example of this type of research
is the study of the epidemic of progressive neurodegenerative disease on
Guam.