Our research interests include an evaluation of the neurotoxic effects aluminum
on CNS and brain-specific gene expression, including the control of chromatin
structure, the influence of epigenetic and ancillary chromatin modifications
that include methylation, phosphorylation and acetylation, factors involving
the initiation and rate of RNA transcript synthesis and the processing,
transport, stability, longevity and targeting of DNA transcription products
in the normally aging human brain and in neurodegenerative disorders, including
Alzheimer's disease (AD).
Aluminum can perturb the genetic integrity of the CNS in mammals and humans and in many experimental systems both in vitro and in vivo. We have shown that the deleterious effects of aluminum on gene activity can be compartmentalized to active chromatin subfractions. Gene expression at the level of RNA message transcription appears to represent one prominent target for aluminum genotoxicity leading to an impairment in the ability of RNA polymerases and DNA sequences to adequately read out genetic information. For example, results from our laboratory have indicated that in experimental aluminum encephalopathy (EAE) and AD there occurs a marked deficit in the transcription of the single-copy, neuron-specific neurofilament light (NFL) chain gene whose gene product supplies a critical component of both the axonal architecture and the shape of the neuron.
- McLachlan, D.R., Kruck, T.P.A. and W.J. Lukiw. Environmental Factors in Alzheimer's Disease; in Alzheimer's and Parkinson's Disease, edited by H.J. Altman and B.N. Altman, pgs. 101-114, Plenum Press, New York, (1988).
- Lukiw, W.J., Kruck, T.P.A. and D.R.C. McLachlan. Linker Histone-DNA Complexes; Enhanced Stability in the Presence of Aluminum Lactate and Implications for Alzheimer's Disease. FEBS Letters, 253:59-62, (1989).
- McLachlan, D.R.C., Lukiw, W.J., and T.P.A. Kruck. New Evidence for an Active Role of Aluminum in Alzheimer's Disease. Can. J. Neurolog. Sci., 16:490-497 (1989).
- Crapper McLachlan, D.R., Lukiw, W.J., and T.P.A. Kruck. Aluminum, Altered Transcription and the Pathogenesis of Alzheimer's Disease. Env. Geochem. and Health, 12:143-154 (1990).
- Lukiw, W.J., et al. Nuclear Compartmentalization of Aluminum in Alzheimer's Disease (AD). Neurobiology of Aging 13:115-121 (1992).
- Lukiw, W.J., St. George-Hyslop, P. and D.R. McLachlan. Chromatin Structure, Gene Expression and Nuclear Aluminum in Alzheimer's Disease. in Basic and Clinical Aspects of Neuroscience, Volume 6, Regulation of Gene Expression and Brain Function, Sandoz Publications 6:31-45 (1994).
- Lukiw, W.J., and D.R. McLachlan. Neurotoxicology of Aluminum in Handbook of Neurotoxicology II: Effects and Mechanisms, edited by L. Chang and R. Dyer, Marcel Dekker, New York, 4:105-142 (1995).
- Lukiw, W.J., Rogaev, E.I, and N.G. Bazan. Synaptic and Cytoskeletal RNA Message Levels in Sporadic Alzheimer Neocortex. Alzheimer's Research 2:221-228 (1996).
- Lukiw, W.J. Alzheimer's Disease and Aluminum. in Mineral and Metal Neurotoxicology, edited by Masayuki Yasui, Michael Strong, Kiichiro Ota and Anthony Verity, CRC Press, New York, 113-126 (1997).
- Lukiw, W.J., et al. Aluminum Inhibits Run-On Transcription in Human Neocortex - Implications for Alzheimer's Disease, submitted (1998).
- Lukiw, W.J. Aluminum and gene transcription in Alzheimer's disease and related neurodegenerative disorders. J. Trace Elements in Exp. Med. 11:419-420 (1998).
- Lukiw, W.J., LeBlanc, H.J., Carver L.A., McLachlan, D.R.C. and N. G. Bazan. Run on gene transcription in human neocortical nuclei - inhibition by nanomolar aluminum and implications for neurodegenerative disease. J. Molec. Neurosci. 11:67-78 (1998).
- Lukiw, W.J., and N. G. Bazan. " Aluminum Impairs Transcription from RNA and DNA Templates" in Proceedings of the Vth Conference of the International Society for Trace Element Research in Humans (ISTERH), 26-30th September 1998, Lyon France. Edited by M. Bost and S. Gamon, Smith-Gordon Publishers, London (1999).
- Lukiw, W.J., Carver L.A., LeBlanc, H.J., and N. G. Bazan. "Analysis of 1184 Genes in Alzheimer CA1 Hippocampus Using High Density cDNA Arrays: cPLA2, ßAPP and IL-1 Precursor Upregulation and Deficits in Zinc-Requiring Transcription Factors". Alzheimer Reports 3:161-167 (2000).
- Lukiw, W.J., "Aluminum and Gene Transcription in the Mammalian Central Nervous System - Implications for Alzheimer's Disease" in Aluminum and Alzheimer's Disease, the Science that Describes the Link, C. Exley, (Editor), Elsevier Science B. V. (2001)
For further information:
Dr. Walter J. Lukiw, Ph.D.,
LSU Neuroscience Center and Department of Ophthalmology
Louisiana State University Health Sciences Center
2020 Gravier Street, Suite 8B8
New Orleans LA 70112-2272
TEL (504) 599-0842
FAX (504) 599-0891
Mail to: email@example.com