Perspective and Direction for Future Developments on Neurotraumatic and Neurodegenerative Diseases

  • Akhlaq A. FarooquiEmail author


Neurotraumatic and neurodegenerative diseases are mediated by synergistic action of excitotoxicity, oxidative stress, neuroinflammation, and misfolding and deposition of specific proteins in the brain tissue (Fig. 10.1) (Farooqui, 2009a). Among neurotraumatic diseases, the onset of stroke may be modulated by age, genes, diet, and lifestyle. Spinal cord injury (SCI) and traumatic brain injury (TBI) are caused by mechanical insults to the spinal cord and brain tissues (Farooqui and Horrocks, 2007), whereas stroke is a metabolic insult induced by severe reduction or blockade in cerebral blood flow. In contrast, neurodegenerative diseases occur in familial and sporadic forms. Familial mutations play an important role in protein misfolding and aggregation, but the majority of cases of neurodegenerative diseases are sporadic, indicating that other factors namely age, diet, lifestyle may also contribute to the pathogenesis of neurodegenerative diseases (Farooqui and Horrocks, 2007).


Traumatic Brain Injury Spinal Cord Injury Single Photon Emission Compute Tomography Neurodegenerative Disease Alzheimer Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Bass SD, Chen WK, Mulkem RV, Bakshi R (2006) Magnetic resonance imaging of iron deposition in neurological disorders. Top Magn Reson Imaging 17:31–40CrossRefGoogle Scholar
  2. Block ML, Hong J-S (2005) Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76:77–98PubMedCrossRefGoogle Scholar
  3. Bray GA, Nielsen SJ, Popkin BM (2004) Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 79:537–543PubMedGoogle Scholar
  4. Brookmeyer R, Gray S, Kawas C (1998) Projections of Alzheimer’s disease in the United State and public health impact of delaying disease onset. Am J Public Health 88:1337–1342PubMedCrossRefGoogle Scholar
  5. Caroli A, Frisoni GB (2009) Quantitative evaluation of Alzheimer’s disease. Expert Rev Med Devices 6:569–588PubMedCrossRefGoogle Scholar
  6. Chen L, Wei Y, Wang X, He R (2009) D-Ribosylated Tau forms globular aggregates with high cytotoxicity. Cell Mol Life Sci 66:2559–2571PubMedCrossRefGoogle Scholar
  7. Chen L, Wei Y, Wang X, He R (2010) Ribosylation rapidly induces alpha-synuclein to form highly cytotoxic molten globules of advanced glycation end products. PLoS One 5(2):e9052PubMedCrossRefGoogle Scholar
  8. Cogan JF, Mitchell OS (2003) Perspective from the President’s commission on Social Security Reform. J Econ Perspect 7:149–172CrossRefGoogle Scholar
  9. Cohen AD, Price JC, Weissfeld LA, James J, Rosario BL, Bi W, Nebes RD, Saxton JA, Snitz BE, Aizenstein HA, Wolk DA, Dekosky ST, Mathis CA, Klunk WE (2009) Basal cerebral metabolism may modulate the cognitive effects of Abeta in mild cognitive impairment: an example of brain reserve. J Neurosci 29:14770–14778PubMedCrossRefGoogle Scholar
  10. Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O‘Keefe JH, Brand-Miller J (2005) Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr 81:341–354PubMedGoogle Scholar
  11. Culmsee C, Landshamer S (2006) Molecular insights into mechanisms of the cell death program: role in the progression of neurodegenerative disorders. Curr Alzheimer Res 3:269–283PubMedCrossRefGoogle Scholar
  12. de Leon MJ, DeSante S, Zinkowski R, Kerkman D, DeBermadis J, Li J, Lair L, Reiberg B, Tsui W, Rusinnek H (2004) MRI and CSF studies in the early diagnosis of Alzheimer’s disease. J Intern Med 256:205–223PubMedCrossRefGoogle Scholar
  13. Eaton SB (2006) The ancestral human diet: what was it and should it be a paradigm for contemporary nutrition? Proc Nutr Soc 65:1–6PubMedCrossRefGoogle Scholar
  14. Farooqui AA, Horrocks LA (2007) Glycerophospholipids in brain. Springer, New York, NYCrossRefGoogle Scholar
  15. Farooqui AA, Horrocks LA, Farooqui T (2007a) Modulation of inflammation in brain: a matter of fat. J Neurochem 101:577–599PubMedCrossRefGoogle Scholar
  16. Farooqui AA, Ong WY, Horrocks LA, Chen P, Farooqui T (2007b) Comparison of biochemical effects of statins and fish oil in brain: the battle of the titans. Brain Res Rev 56:443–471PubMedCrossRefGoogle Scholar
  17. Farooqui AA, Ong WY, Horrocks LA (2008) Neurochemical aspects of excitotoxicity. Springer, New York, NYGoogle Scholar
  18. Farooqui T, Farooqui AA (2009) Aging: an important factor for the pathogenesis of neurodegenerative diseases. Mech Aging Dev 130:203–215PubMedCrossRefGoogle Scholar
  19. Farooqui AA (2009a) Hot topics in neural membrane lipidology. Springer, New York, NYCrossRefGoogle Scholar
  20. Farooqui AA (2009b) Beneficial effects of fish oil on human brain. Springer, New York, NYCrossRefGoogle Scholar
  21. Finch CE, Sapolsky RM (1999) The evolution of Alzheimer disease, the reproductive schedule, and apoE isoforms. Neurobiol Aging 20:407–428PubMedCrossRefGoogle Scholar
  22. Fleming JJ, England PM (2010) AMPA receptors and synaptic plasticity: a chemist’s perspective. Nat Chem Biol 6:89–97PubMedCrossRefGoogle Scholar
  23. Gilgun-Sherki Y, Melamed E, Offen D (2006) Anti-inflammatory drugs in the treatment of neurodegenerative diseases: current state. Curr Pharmaceut Des 12:3509–3519CrossRefGoogle Scholar
  24. Gomez-Pinilla F (2008) Brain foods: the effects of nutrients on brain function. Nat Neurosci Rev 9:568–578CrossRefGoogle Scholar
  25. Hampel H, Burger K, Teipel SJ, Bokde AL, Zetterberg H, Blennow K (2008) Core candidate neurochemical and imaging biomarkers of Alzheimer’s disease. Alzheimers Dement 4:38–48PubMedCrossRefGoogle Scholar
  26. Handley OJ, Naji JJ, Dunnett SB, Rosser AE (2006) Pharmaceutical, cellular and genetic therapies for Huntington’s disease. Clin Sci (Lond) 110:73–88CrossRefGoogle Scholar
  27. Hayashi T, Shoji M, Abe K (2006) Molecular mechanisms of ischemic neuronal cell death–with relevance to Alzheimer’s disease. Curr Alzheimer Disease 3:351–358CrossRefGoogle Scholar
  28. Henley SM, Bates GP, Tabrizi SJ (2005) Biomarkers for neurodegenerative diseases. Curr Opin Neurol 18:698–705PubMedCrossRefGoogle Scholar
  29. Hodes RJ (2006) Public funding for Alzheimer’s disease research in United States. Nat Med 12:770–773PubMedCrossRefGoogle Scholar
  30. Jin H, Randazzo J, Zhang P, Kador PF (2010) Multifunctional antioxidants for the treatment of age-related diseases. J Med Chem 53:1117–1127PubMedCrossRefGoogle Scholar
  31. Kamphuis PJ, Wurtman RJ (2009) Nutrition and Alzheimer’s disease: pre-clinical concepts. Eur J Neurol 16(Suppl 1):12–18PubMedCrossRefGoogle Scholar
  32. Langstrom B, Andren PE, Lindhe O, Svedberg M, Hall H (2007) In vitro imaging techniques in neurodegenerative diseases. Mol Imaging Biol 9:161–175PubMedCrossRefGoogle Scholar
  33. Lu Y, Hong S, Gotlinger K, Serhan CN (2006) Lipid mediator informatics and proteomics in inflammation-resolution. Sci World J 6:589–614CrossRefGoogle Scholar
  34. Mattson MP, Duan W, Pedersen WA, Culmsee C (2001) Neurodegenerative disorders and ischemic brain diseases. Apoptosis 6:69–81PubMedCrossRefGoogle Scholar
  35. Migliore L, Fontana I, Colognato R, Coppede F, Siciliano G, 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 26:587–595PubMedCrossRefGoogle Scholar
  36. Miranda HV, Outerio TF (2009) The sour side of neurodegenerative disorders: the effects of protein glycation. J Pathol Dec 31 [Epub ahead of print]Google Scholar
  37. Molteni R, Bernard RJ, Ying Z, Roberts CK, Gomez-Pinilla F (2002) A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 112:803–814PubMedCrossRefGoogle Scholar
  38. Naigai Y, Fujikake N, Popiel HA, Wada K (2010) Induction of molecular chaperones as a therapeutic strategy for the polyglutamine diseases. Curr Pharm Biotechnol Fab 16 [Epub ahead of print]Google Scholar
  39. Nile DY, Xu G, Ahmed S, Xiao ZC (2007) DNA vaccine and the CNS axonal regeneration. Curr Pharm Des 13:2500–2506Google Scholar
  40. Ono M (2007) Molecular imaging of beta-amyloid plaques in the brain. Brain Nerve 59:233–240PubMedGoogle Scholar
  41. Palop JJ, Chin J, Mucke L (2006) A network dysfunction perspective on neurodegenerative diseases. Nature 443:768–773PubMedCrossRefGoogle Scholar
  42. Pettegrew JW, Klunk WE, Kanal E, Panchalingam K, McClure RJ (1995) Changes in brain membrane phospholipid and high-energy phosphate metabolism precede dementia. Neurobiol Aging 16:973–975PubMedCrossRefGoogle Scholar
  43. Revill P, Moral MA, Prous JR (2006) Impaired insulin signaling and the pathogenesis of Alzheimer’s disease. Drug Today 42:785–790CrossRefGoogle Scholar
  44. Schmitt HP (2006) epsilon-Glycation, APP and Abeta in ageing and Alzheimer disease: a hypothesis. Med Hypotheses 66:698–906CrossRefGoogle Scholar
  45. Schneider P, Hampel H, Buerger K (2009) Biological marker candidates of Alzheimer’s disease in blood, plasma, and serum. CNS Neurosci Ther 15:358–374PubMedCrossRefGoogle Scholar
  46. Simopoulos AP (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 56:365–379PubMedCrossRefGoogle Scholar
  47. Simopoulos AP (2006) Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 60:502–507PubMedCrossRefGoogle Scholar
  48. Small GW, Bookheimer SY, Thompson PM, Cole GM, Huang SC, Kepe V, Barrio JR (2008) Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurol 7:161–172PubMedCrossRefGoogle Scholar
  49. Stranahan RS, Normal ED, Lee K, Cutler RG, Telljohan RS, Egan JM, Mattson MP (2008) Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus 18:1085–1088PubMedCrossRefGoogle Scholar
  50. Takeuchi M, Yamagishi S, Iwaki M, Nakamura K, Imaizumi T (2004) Advanced glycation end product (age) inhibitors and their therapeutic implications in diseases. Int J Clin Pharmacol 24:95–101Google Scholar
  51. Tan DX, Manchester LC, Sainz R, Mayo JC, Alvares FL, Reiter RJ (2003) Antioxidant strategies in protection against neurodegenerative disorders. Expert Opin Ther Patents 13:1513–1543CrossRefGoogle Scholar
  52. Thobois S, Guillouet S, Bronssolle E (2001) Contributions of PET and SPECT to the understanding of the pathophysiology of Parkinson’s disease. Neurophysiol Clin 31:321–340PubMedCrossRefGoogle Scholar
  53. Trojanowski JQ (2008) PENN neurodegenerative disease research – in the spirit of Benjamin Franklin. Neurosignals 16:5–10PubMedCrossRefGoogle Scholar
  54. Vemuri P, Wiste HJ, Weigand SD, Shaw LM, Trojanowski JQ, Weiner MW, Knopman DS, Petersen RC, Jack CR Jr Alzheimer’s Disease Neuroimaging Initiative (2009) MRI and CSF biomarkers in normal, MCI, and AD subjects: predicting future clinical change. Neurology 73:294–301PubMedCrossRefGoogle Scholar
  55. Wang JY, Wen LL, Huang YN, Chen YT, Ku MC (2006) Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidative stress and indirect protection via suppression of glia-mediated inflammation. Curr Pharmaceut Des 12:3521–3533CrossRefGoogle Scholar
  56. Waza M, Adachi H, Katsuno M, Minamiyama M, Tanaka F, Doyu M, Sobue G (2006) Modulation of Hsp90 function in neurodegenerative disorders: a molecular-targeted therapy against disease-causing protein. J Mol Med 84:635–646PubMedCrossRefGoogle Scholar
  57. Wood PL (1998) Neuroinflammation: mechanisms and management. Humana Press, Totowa, NJGoogle Scholar
  58. Wurtman RJ, Cancev W, Sakamoto T, Ulus IH (2009) Use of phosphatide precursors to promote synaptogenesis. Annu Rev Nutri 29:59–87CrossRefGoogle Scholar
  59. Xie CW (2004) Calcium-regulated signaling pathways: role in amyloid β-induced synaptic dysfunction. Neuromolecular Med 6:53–64PubMedCrossRefGoogle Scholar
  60. Xu G, Nie DY, Chen JT, Wang CY, Yu FG, Sun L, Luo XG, Ahmed S, Xiao ZC (2004) Recombinant DNA vaccine encoding multiple domains related to inhibition of neurite outgrowth: a potential strategy for axonal regeneration. J Neurochem 91:1018–1023PubMedCrossRefGoogle Scholar
  61. Yan SD, Bierhaus A, Nawroth PP, Stern DM (2009) RAGE and Alzheimer’s disease: a progression factor for amyloid-beta-induced cellular perturbation? J Alzheimer Res 16:833–843Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Molecular and Cellular BiochemistryThe Ohio State UniversityColumbusUSA

Personalised recommendations