Aluminium and the nucleus of nerve cells.

S x ~ , B i i and Chappelll have reviewed in The Lancet neurochemical aspects of the interaction of aluminium (Al) with physiological ligands, emphasishg the preference of this neurotoxin for association with oxygen donor p u p s , especially cytosolic phosphates. We would add to their argument the potential for Al to interact with nucleic acid polyphosphates. This is of neurotoxological interest because Al accumulates within affected neocomcal nuclei in Alzheimer di~ease.~ The cell nucleus, with its phosphate-containing DNA and RNA, has the highest phosphate density--and thus the highest potential Al biaing capaciq-of any cellular organelle. Neuronal nuclei, with their large size, extensive euchromatisation, the fasur digestion kinetics when exposed to nuclease, high tmmdptional output, and extensive nuclear pore complex system, are especially susceptible to A! intoxication. Al interacts strongly with chnnnatin and DNA and this assodation has harmful effects on nuclear metabolism. There is preferential biding of Al within the nucleuslU and d t e d with raised nuclear Al levels is decreased cell division and DNA synthesis,6 and an inaease in DNA replication erron and otha effects at the chromosomal, DNA, and RNA levels* suggest Al-induced irnp+ment of nucleic acid metabo-d, ultimately, a deficit in the uansmission of genetic information. The small ionic radius and high positive charge density of Al may favour the ttanslocation of this cation acmss endothelial, glial, or neuronal manbrane Concentratiocls of phospHate are 2 mmol/l in plasma, 10 mrnol/l in the cytosol, and at least 50 mmol/l withiri the nucleus, so the nucleus provides a high &ty, high capacity Sink which traps aluminium.