In Alzheimer s disease and

Rather scanty evidence exists for the participation of free radicals in Alzheimer s disease and Down s syndrome. However, more recendy, reports have appeared that suggest possible free-radical involvement in the pathogenesis of these two conditions. Zemlan et al. (1989) repotted that the activity of the free-radical scavenging enzyme, SOD, was significantly increased in fibroblast cell lines derived from familial Alzheimer s and Down s patients. They hypothesized that the elevation in SOD activity observed in the Alzheimer patients supports the theory that paired helical filaments are formed by free-radical hydroxylation of proline residues. They further su ested that SOD levels might also be increased in the brains of Alzheimer s and Down s patients, and that the increase in SOD may reflect an enhanced generation of free radicals. 

Despite the indications for involvement of free radicals in Alzheimer s disease and Down s syndrome pathogenesis summarized above, more evidence is needed to establish a role for free-radical mechanisms in these disease processes. If free radicals can be demonstrated to play a role in the pathogenesis of Alzheimer s disease and Down s syndrome, then this would set the stage for chronic therapy with antioxidants in these disease states. 

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Weinreb PH, Zhen W, Poon AW, Conway KA, Lansbury PT Jr. NACP, a protein implicated in Alzheimer s disease and learning, is natively unfolded. Biochemistry 1996 35 13709-13715. 

Harper JD, Lansbury PT Jr. Models of amyloid seeding in Alzheimer s disease and scrapie mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. Annu Rev Biochem 1997 66 385-407. 

Pettigrew JW, Levine J and McClure RJ (2000). Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties Relevance for its mode of action in Alzheimer s disease and geriatric depression. Molecular Psychiatry, 5, 626-632. 

Singleton, A. B., Gibson, A. M., McKeith, I. G. et al. Alpha2-macroglobulin polymorphisms in Alzheimer s disease and dementia with Lewy bodies. Neuroreport 10 1507-1510, 1999. 

Jarrell, ). T., and Lansbury, P. T.,Jr. (1993). Seeding one-dimensional crystallization of amyloid A pathogenic mechanism in Alzheimer s disease and scrapie Cell 73, 1055-1058. 

Table 10.2 Potential therapeutic strategies in Alzheimer s disease and dementia... 

Fig. 10.9 Pathogenic factors acting on neuronal targets in Alzheimer s disease and the process of pharmacological treatment. ABP, amyloid 3-protein APP, ABP precursor protein CHO, choies-teroi NFT-Tau, neurofibriiiary tangie tau...

Olichney, J.M., Hansen, L.A., Galasko, D., et al. (1996) The apolipoprotein E epsylon-4 allele is associated with increased neuiific plaques and cerebral amyloid angiopathy in Alzheimer s disease and Lewy body variant. Neurology, 47, 190-196. 

The main limitation of the coordination ROP of lactones remains the toxicity of the metal. For instance, aluminum derivatives are suspected to be involved in Alzheimer s disease, and tin(ll) bis-(2-ethyUiexanoate) is cytotoxic. In order to overcome this drawback, many groups have investigated the replacement of tin and aluminum alkoxides by initiators based on less toxic metals such as magnesium [54, 55] and calcium [56, 57] alkoxides. 

Ahmed, N., Ahmed, U., Thornalley, P. J., Hager, K., Fleischer, G., and Munch, G. (2005). Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer s disease and link to cognitive impairment. ]. Neurochem. 92, 255-263. 

Bar, K. J., Franke, S., Wenda, B., Muller, S., Kientsch-Engel, R., Stein, G., and Sauer, H. (2002). Pentosidine and N(epsilon)-(carboxymethyl)-lysine in Alzheimer s disease and vascular dementia. Neurobiol. Aging 24, 333-338. 

Frey WH, Liu J, Thorne RG, et al Intranasal delivery of 125 1-labeled nerve growth factor to the brain via the olfactory route, in Research Advances in Alzheimer s Disease and Related Disorders. Edited by Iqbal K, Mortimer JA, Winblad B, et al. Chichester, England, Wiley, 1995, pp 329-335 Eriedman E, Gershon S Effect of lithium on brain dopamine. Nature 243 520-521, 1973... 

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Newman SC The prevalence of depression in Alzheimer s disease and vascular dementia in a population sample. J Affect Disord 52 169-176, 1999 Nibuya M, Rydelek-Fitzgerald L, Russell DS, et al Induction of BDNE and trkB by electroconvulsive seizure regional regulation and role of CREB. Soc Neurosci 24 1312, 1994... 

Butterfield DA, Sultana R. 2007. Redox proteomics identification of oxidatively modified brain proteins in Alzheimer s disease and mild cognitive impairment Insights into the progression of this dementing disorder. J Alzheimers Dis 12 61-72. 

Magaki S, Raghavan R, Mueller C, Oberg KC, Vinters HV, Kirsch WM. 2007. Iron, copper, and iron regulatory protein 2 in Alzheimer s disease and related dementias. Neurosci Lett 418 72-76. 

Berman K. and Brodaty H. (2004). Tocopherol (vitamin E) in Alzheimer s disease and other neu-rodegenerative disorders. CNS Drugs 18 807-825. 

Migliore L., Fontana I., Colognato R., Coppede F., Siciliano G., and Murri L. (2005). Searching for the role and the most suitable biomarkers of oxidative stress in Alzheimer s disease and in other neurodegenerative diseases. Neurobiol. Aging 26 587-595. 

The microtubule-associated-protein tau is a component of the neurofibrillary tangles in Alzheimer s disease and a target of S100A1. PC 12 cells devoid of S100A1 were shown to be more resistant to A(3(25-35) peptide-mediated cell death and have lower levels of intracellular amyloid precursor protein (APP) (Zimmer et al., 2005). 

Boom A, Pochet R, Authelet M, Pradier L, Borghgraef P, Van Leuven F, Heizmann CW, Brion JP. 2004. Astrocytic calcium/zinc binding protein S100A6 over expression in Alzheimer s disease and in PS1/APP transgenic mice models. Biochim Biophys Acta 1742(1—3) 161—168. 

Pharmaceutical researchers in Japan find that an N-benzylpiperazine derivative stimulates acetylcholine neurotransmitter. This discovery subse-quentely leads to the discovery of donepezil (Ari-cept), which helps ward off memory loss in Alzheimer s disease and age-related dementias. 

Bliwise DL (2004) Sleep disorders in Alzheimer s disease and other dementias. Clin Cornerstone 6 (Suppl 1A) S16-S28... 

Zapatero MD, Garcia de Jalon A, Pascual F, et al. 1995. Serum aluminum levels in Alzheimer s disease and other senile dementias. Biol Trace Elem Res 47 235-240. 

Neuroinflammation in Alzheimer s Disease and Parkinson s Disease Are Microglia Pathogenic in Either Disorder ... 

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