The Guam Cycad Toxin Methylazoxymethanol Damages Neuronal DNA and Modulates Tau mRNA Expression and Excitotoxicity

Sports and trauma in amyotrophic lateral sclerosis revisited

“…Induction of acquired nucleic acid changes that persist long after the exposure is over may bring a cell's nucleic acids closer to the transforming change that may trigger onset of ALS [23]. This line of reasoning is consistent with Spencer's proposal of the most likely mechanism for delayed-onset western Pacific ALS, years after putative ingestion of Cycad toxins [24]. Finally, it may be appropriate to include the possibility of an interaction between systemically-ingested and locallyingested toxins.…”

An Evidence-Based Medicine Approach to the Evaluation of the Role of Exogenous Risk Factors in Sporadic Amyotrophic Lateral Sclerosis

“…Reduction in the ability to detoxify smoking-related carcinogens by some post-menopausal women [32] may explain the increased mortality from ALS predominantly in women over 65 in a recent report [33]. In additional support of a carcinogen, or alkylating agent, as possibly involved in causing some forms of ALS, Spencer [34,35] currently favors methylazoxymethanol, a potent alkylating agent, the aglycone of cycasin, as the primary mechanism for the long-latency induction of Western Pacific ALS. He postulates that methylazoxymethanol may produce post-mitotic DNA damage and interfere with DNA repair, up-regulate the expression of Ù mRNA by itself or in conjunction with an endogenous excitotoxic agent (neurotransmitter glutamate), and thus promote the accumulation of Ù protein and neuronal degeneration in Western Pacific ALS/PDC.…”

Distribution and Cellular Localization of KCC2 in the Ferret Neocortex

“…Using immunohistochemistry, we show a shift in KCC2 expression during development, being high in the subplate at P0, repositioning into a subtle laminar pattern in the neocortex at P7-P14, and becoming homogeneous at P35. KCC2 colocalizes with neuronal markers in the developing and mature cerebral cortex of normal ferrets and those treated with MAM, but shows a differential pattern of expression at different ages and lo-which selectively disrupts the proliferation of specific neuronal cell populations in S-phase at the time of administration [11][12][13]. After treatment with MAM in pregnant ferrets during corticogenesis, although the offspring are relatively normal in appearance, a number of features in their cortical architecture and function are altered.…”