Open Access
Subscription Access
Open Access
Subscription Access
Alzheimer’s Disease Pathophysiology and its Implications
Subscribe/Renew Journal
Alzheimer’s disease (AD) is a destructive neurodegenerative disorder characterized by progressive memory defeat and impairment in behavior. Accordingly, although there is presently no “cure” for Alzheimer’s disease. A large number of potential therapeutic interventions have emerged that are designed to correct loss of presynaptic cholinergic function. A few of these compounds have confirmed in delaying the deterioration of symptoms of Alzheimer’s disease, a valuable treatment target considering the progressive nature of the disease. This review summarizes the main underlying neurobiological mechanisms in AD, including the theory with emphasis on amyloid peptide, cholinergic hypothesis, the role of tau protein, and the involvement of oxidative stress in Alzheimer. We also shed light on the inflammatory process involved in the progression of Alzheimer along with its recent advances in the treatment.
Keywords
Alzheimer, Amyloid Peptide, Tau Protein, Inflammatory Process, Treatment.
Subscription
Login to verify subscription
User
Font Size
Information
- Anand R, Gill KD, Malhdi AA. Therapeutics of Alzheimer’s disease: past, present and future. Neuropharmacology 2014; 76:27-50.
- Selkoe DJ. Normal and abnormal biology of the beta-Amyloid Precursor Protein. Annu Rev Neurosci 1994; 17:489–517.
- Anderson JP, Chen Y, Kim KS, Robakis NK. An alternative secretasecleavage produces soluble Alzheimer amyloid precursor protein containing a potentially amyloidogenic sequence. J Neurochem 1992; 59:2328–31.
- Blasko I, et al. Costimulatory Effects of Interferon-g and Interleukin-1b or Tumor Necrosis Factor a on the Synthesis of Ab1-40 and Ab1-42 by Human Astrocytes. Neurobiol Dis 2000; 7:682–9.
- Murphy MP, LeVine H. Alzheimer’s disease and the b-Amyloid peptide. J Alzheimer’s Dis 2010; 19:311.
- Alonso AC, Grundke-Iqbal I, Iqbal K. Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat Med 1996; 2:7837.
- Alonso AC et al. Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease. Proc Natl Acad Sci U S A 1994;91: 5562–6.
- Schmitt H, Gozes I, Littauer UZ. Decrease in levels and rates of synthesis of tubulin and actin in developing rat brain. Brain Res 1977; 121:327–42.
- Avila J, et al. Role of tau protein in both physiological and pathological conditions. Physiol Rev 2004; 84:361–84.
- Ebneth A, et al. Overexpression of Tau Protein Inhibits Kinesin-dependent Trafficking of Vesicles, Mitochondria, and Endoplasmic Reticulum: Implications for Alzheimer’s Disease. J Cell Biol 1998; 143:777–94.
- Gong C-X, Iqbal K. Hyperphosphorylation of microtubule-Associated protein Tau: A promising therapeutic target for Alzheimer disease. Curr Med Chem 2008; 15:2321–8.
- Simi_c G, et al. Tau Protein Hyperphosphorylation and aggregation in Alzheimer’s disease and other tauopathies, and possible neuroprotective strategies. Biomolecules 2016;6.
- Griffin WS et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci U S A 1989; 86:7611–5.
- Rogers J, et al. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer’s disease. Neurobiol Aging 1988;9:339-49.
- Miguel-Alvarez M, et al. Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer’s disease: a systematic review and meta-analysis of treatment effect. Drugs Aging 2015; 32:139–47.
- McGeer PL, Rogers J. Anti-inflammatory agents as a therapeutic approach to Alzheimer’s disease. Neurology 1992; 42:447–9.
- Plassman BL, et al. Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias. Neurology 2000; 55:1158–66.
- Quintanilla RA, et al. Interleukin-6 induces Alzheimer-type phosphorylation of tau protein by deregulating the cdk5/p35 pathway. Exp Cell Res 2004; 295:245–57.
- Terry AV Jr, Buccafusco JJ: The cholinergichypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther 2003; 306: 821–827.
- Schaeffer EL, Gattaz WF: Cholinergic and glutamatergic alterations beginning at the early stages of Alzheimer disease: participation of the phospholipase A2 enzyme. Psychopharmacology (Berl) 2008; 198: 1–27.
- Fisher A: M1 muscarinic agonists target major hallmarks of Alzheimer’s disease – an update. Curr Alzheimer Res 2007; 4: 577–580.
- Shen J, Wu J: Nicotinic cholinergic mechanisms in Alzheimer’s disease. Int Rev Neurobiol 2015; 124: 275–292.
- Dong XX, Wang Y, Qin Z: Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacol Sin 2009; 30: 379–387.
- Navarro A, Boveris A: The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 2007; 292:C670–C686.
- Cummings JL, Doody R, Clark C: Disease modifying therapies for Alzheimer disease: challenges to early intervention. Neurology 2007; 69: 1622–1634.
- Wu LG, Saggau P: Presynaptic inhibition of elicited neurotransmitter release. Trends Neurosci 1997; 20: 204–212.
- Roberson ED, et al: Reducing endogenoustau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science 2007; 316: 750–754.
- Lin MT, Beal MF: Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006; 443: 787–795.
- Rafii MS, Aisen PS: Recent developments in Alzheimer’s disease therapeutics. BMC Med 2009; 7: 7.]
- Zhao Y, Zhao B: Oxidative stress and the pathogenesis of Alzheimer’s disease. Oxid Med Cell Longev 2013; 2013: 316523.
- Salomone S, et al. New pharmacological strategies for treatment of Alzheimer’s disease: focus on disease modifying drugs. Br J Clin Pharmacol 2012; 73:504-17.
- Pei JJ, Ogren MS, Winblad B. Neurofibrillary degeneration in Alzheimer’s disease: from molecular mechanisms to identification of drug targets. Curr Opinion Psychiatry 2008; 21:555-61.
- Seren L, Coma M, Rodr M, Guez L. A novel GSK-3α inhibitor reduces Alzheimer’s pathology and rescues neuronal loss in vivo. Neurobiol Dis 2009; 35:359-67.
- Swerdlow RH, Khan SM. A mitochondrial cascade hypothesis for sporadic Alzheimer’s disease. Med Hypotheses 2004; 63:8–20.
- Nordberg A, Darreh-Shori T, Svenson A, Guan Z. AChE and BuChE activities in CSF of mild AD patients following 12 mo of rivastigmine treatment. J Neurol Sci 2001; 187: P0144.
Abstract Views: 227
PDF Views: 0