Academia.eduAcademia.edu

Outline

Alzheimer's disease: new diagnostic and therapeutic tools

2008, Immunity & Ageing

https://doi.org/10.1186/1742-4933-5-7

Abstract

On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lectures of M. Racchi on History and future perspectives of Alzheimer Biomarkers and of G. Scapagnini on Cellular Stress Response and Brain Ageing are summarized. Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease, which in Western society mainly accounts for clinica dementia. AD prevention is an important goal of ongoing research. Two objectives must be accomplished to make prevention feasible: i) individuals at high risk of AD need to be identified before the earliest symptoms become evident, by which time extensive neurodegeneration has already occurred and intervention to prevent the disease is likely to be less successful and ii) safe and effective interventions need to be developed that lead to a decrease in expression of this pathology. On the whole, data here reviewed strongly suggest that the measurement of conformationally altered p53 in blood cells has a high ability to discriminate AD cases from normal ageing, Parkinson's disease and other dementias. On the other hand, available data on the involvement of curcumin in restoring cellular homeostasis and rebalancing redox equilibrium, suggest that curcumin might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation, such as AD.

References (33)

  1. Vasto S, Candore G, Listì F, Balistreri CR, Colonna-Romano G, Mala- volta M, Lio D, Nuzzo D, Mocchegiani E, Di Bona D, Caruso C: Inflammation, Genes and Zinc in Alzheimer's disease. Brain Research Review 2008, 58:96-105.
  2. Vasto S, Candore G, Duro G, Lio D, Grimaldi MP, Caruso C: Alzhe- imer's disease and genetics of inflammation: a pharmacoge- nomic vision. Pharmacogenomics 2007, 8:1735-45.
  3. Weksler ME: The immunotherapy of Alzheimer's disease. Immun Ageing 2004, 1:2.
  4. Tobinick EL, Gross H: Rapid cognitive improvement in Alzhe- imer's disease following perispinal etanercept administra- tion. J Neuroinflammation 2008, 5:2.
  5. Bieler S, Soto C: Beta-sheet breakers for Alzheimer's disease therapy. Curr Drug Targets 2004, 5:553-8.
  6. Licastro F, Caruso C: Is immunotherapy an effective treatment for Alzheimer's disease? Immun Ageing 2004, 1:3.
  7. Blennow K, Hampel H: CSF markers for incipient Alzheimer's disease. Lancet Neurol 2003, 2:605-613.
  8. Thal LJ, Kantarci K, Reiman EM, Klunk WE, Weiner MW, Zetterberg H, Galasko D, Praticò D, Griffin S, Schenk D, Siemers E: The role of biomarkers in clinical trials for Alzheimer's disease. Alzheimer Dis Assoc Disord 2006, 20:6-15.
  9. Crystal HA, Davies P: Toward a plasma marker for Alzheimer disease: Some progress, but still a long way to go. Neurology 2008, 70:586-587.
  10. Frey HJ, Mattila KM, Korolainen MA, Pirttila T: Problems associ- ated with biological markers of Alzheimer's disease. Neuro- chem Res 2005, 30:1501-1510.
  11. Uberti D, Lanni C, Carsana T, Francisconi S, Missale C, Racchi M, Govoni S, Memo M: Identification of a mutant-like conforma- tion of p53 in fibroblasts from sporadic Alzheimer's disease patients. Neurobiol Aging 2006, 27:1193-1201.
  12. Uberti D, Lanni C, Racchi M, Govoni S, Memo M: Conformationally altered p53: a putative peripheral marker for Alzheimer's disease. Neurodegener Dis 2008, 5:209-11.
  13. Lanni C, Uberti D, Racchi M, Govoni S, Memo M: Unfolded p53: a potential biomarker for Alzheimer's disease. J Alzheimers Dis 2007, 12:93-9.
  14. Lanni C, Racchi M, Mazzini G, Ranzenigo A, Polotti R, Sinforiani E, Oli- vari L, Barcikowska M, Styczynska M, Kuznicki J, Szybinska A, Govoni S, Memo M, Uberti D: Conformationally altered p53: a novel Alzheimer's disease marker? Mol Psychiatry 2008, 13:641-647.
  15. Cenini G, Sultana R, Memo M, Butterfield DA: Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE, in brain from subjects with amnestic mild cognitive impairment and Alzheimer's dis- ease. J Cell Mol Med 2008, 12:987-94.
  16. Cenini G, Sultana R, Memo M, Butterfield DA: Effects of oxidative and nitrosative stress in brain on p53 proapoptotic protein in amnestic mild cognitive impairment and Alzheimer disease. Free Radic Biol Med 2008, 45:81-5.
  17. Calabrese V, Scapagnini G, Giuffrida Stella AM, Bates TE, Clark JB: Mitochondrial involvement in brain function and dysfunc- tion: relevance to aging, neurodegenerative disorders and longevity. Neurochem Res 2001, 26:739-764.
  18. Abraham NG, Drummond GS, Lutton JD, Kappas A: The biological significance and physiological role of heme oxygenase. Cell Physiol Biochem 1996, 6:129-168.
  19. Maines MD: The heme oxygenase system and its functions in the brain. Cell Mol Biol 2000, 46:573-585.
  20. Scapagnini G, D'Agata V, Calabrese V, Pascale A, Colombrita C, Alkon D, Cavallaro S: Gene expression profiles of heme oxygenase isoforms in the rat brain. Brain Res 2002, 954:51-56.
  21. Takeda A, Perry G, Abraham NG, Dwyer BE, Kutty RK, Laitinen JT, Petersen RB, Smith MA: Overexpression of heme oxygenase in neuronal cells, the possible interaction with Tau. J Biol Chem 2000, 275:5395-5399.
  22. Schipper HM: Heme oxygenase-1: role in brain aging and neu- rodegeneration. Exp Gerontol 2000, 35:821-830.
  23. Chen K, Gunter K, Maines MD: Neurons overexpressing heme oxygenase-1 resist oxidative stress-mediated cell death. J Neurochem 2000, 75:304-312.
  24. Nakatani N: Phenolic antioxidants from herbs and spices. Bio- factors 2000, 13:141-146.
  25. Scapagnini G, Foresti R, Calabrese V, Giuffrida Stella AM, Green CJ, Motterlini R: Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Mol Pharmacol 2002, 61:554-561.
  26. Scapagnini G, Colombrita C, Amadio M, D'Agata V, Arcelli E, Sapienza M, Quattrone A, Calabrese V: Curcumin activates defensive genes and protects neurons against oxidative stress. Antioxid Redox Signal 2006, 8:395-403.
  27. Chandra V, Pandav R, Dodge HH, Johnston JM, Belle SH, DeKosky ST, Ganguli M: Incidence of Alzheimer's disease in a rural commu- nity in India: the Indo-US study. Neurology 2001, 57:985-989.
  28. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM: Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 2005, 280:5892-5901.
  29. Frautschy SA, Hu W, Miller SA, Kim P, Harris-White ME, Cole GM: Phenolic anti-inflammatory antioxidant reversal of A_- induced cognitive deficits and neuropathology. Neurobiol Aging 2001, 22:993-1005.
  30. Scapagnini G, Butterfield DA, Colombrita C, Sultana R, Pascale A, Calabrese V: Ethyl ferulate, a lipophilic polyphenol, induces HO-1 and protects rat neurons against oxidative stress. Anti- oxid Redox Signal 2004, 6:811-818.
  31. Gómez-Pinilla F: Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci 2008, 9:568-78.
  32. Goel A, Kunnumakkara AB, Aggarwal BB: Curcumin as "Curecu- min": from kitchen to clinic. Biochem Pharmacol 2008, 75:787-809.
  33. Mortimer JA, Borenstein AR: Early-life risk factors for Alzhe- imer's disease. Research and Practice in Alzheimer's Disease 2007, 12:76-80.