Astrocyte metallothioneins (MTs) and their neuroprotective role

I have briefly detailed in this review the role of astrocytes in MeHg neurotoxicity, emphasizing the mechanisms and significance of astrocytic swelling in neuropathological conditions. I have also described the functions of brain MTs and have reported recent observations on their propensity to attenuate cytotoxicity. While it is unclear why three different MT genes are expressed in the brain, this redundancy should allow for greater accumulation of MTs under stressful conditions compared to its accumulation if only a single gene was present.⁹⁰ Another explanation may be that genes encoding functionally identical MTs might be regulated independently, thus permitting cell-specific MT expression. Finally, each of the three MT isoforms may have distinct functions. As discussed herein, astrocytic MTs afford protection from the acute cytotoxic effects of MeHg, reversing the effect of this organometal on RVD and inhibition of taurine release. Whether other vital cellular functions are protected by MTs will have to await future studies, as will the mechanisms associated with MT-induced cellular protection. That the resistance to heavy metal toxicity is closely related to the cellular ability to synthesize MTs, raises interesting questions regarding the potential involvement of heavy metals in neurodegenerating (amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease) under conditions of compromised MT synthesis. Future studies on the expression and regulation of MT genes are likely to culminate in novel strategies for manipulating intracellular MT levels, providing insight to their role in both health and disease.