Alzheimer disease pathophysiology

Lashuel, H. A., Petre, B. M., Wall, J., Simon, M., Nowak, R. J., Walz, T., and Lansbury, P. T., Jr. (2002). Alpha-synuclein, especially the Parkinson s disease-associated mutants, forms pore-like annular and tubular protofibrils./. Mol. Biol. 322,1089-1102. LeVine, H. (1993). Thioflavine T interaction with synthetic Alzheimer s disease beta-amyloid peptides Detection of amyloid aggregation in solution. Protein Sci. 2, 404—410. Lin, H., Bhatia, R., and Lai, R. (2001). Amyloid beta protein forms ion channels Implications for Alzheimer s disease pathophysiology. FASEB J. 15, 2433-2444. Lorenzo, A., and Yankner, B. A. (1994). Beta-amyloid neurotoxicity requires fibril formation and is inhibited by Congo red. Proc. Natl. Acad. Sci. USA 91, 12243-12247. Luhrs, T., Ritter, C., Adrian, M., Riek-Loher, D., Bohrmann, B., Dobeli, H., Schubert, D., and Riek, R. (2005). 3D structure of Alzheimer s amyl o id-( be la) (1—12) fibrils. Proc. Natl. Acad. Sci. USA 102, 17342-17347. 

Giorgio, S., Alessia, L., LUcilla, P., Daniele, T., and Francesso, A. (2006). Treatment of Alzheimer s disease From pharmacology to a better understanding of disease pathophysiology. Mech. Ageing Dev. 127,148-157. 

Fadl NN, Ahmed HH, Booles HF, Sayed AH (2013) Serrapeptase and nattokinase intervention for relieving Alzheimer s disease pathophysiology in rat model. Hum Exp Toxicol 32 721-735... 

Brumback RA, Leech RW (1994) Alzheimer s disease pathophysiology and the hope for therapy, J Okla State Med Assoc 87 103-11. 

Larson ME, Sherman MA, Greimel S, et al. Soluble alpha-syimdein is a novel modulator of Alzheimer s disease pathophysiology. / Neurosci. 2012 32(30) 1Q253-1Q266. 

Sanderson KL, Butler L, Ingram VM. Aggregates of a beta-amyloid peptide are required to induce calcium currents in neuron-Uke human teratocardnoma cells relation to Alzheimer s disease. Brain Res. 1997 744(1) 7-14. lin H, Bhatia R, Lai R. Amyloid beta protein forms ion channels implications for Alzheimer s disease pathophysiology. FASEB. 2001 15(13) 2433-2444. 

Lin H, Bhatia R, Lai R. Amyloid beta protein forms ion channels implications for Alzheimer s disease pathophysiology. FASEB J. 2001 15(13) 2433-2444. 

H. Amiri, K. Saeidi, P. Borhani, A. Manafirad, M. Ghavani and V. Zerbi, Alzheimer s Disease Pathophysiology and Applications of Magnetic Nanoparticles as MRI Theranostic Agents, ACS Chem. NeuroscL, 2013,... 

MT-associated proteins (MAPs) are attached to MTs in vivo and play a role in their nucleation, growth, shrinkage, stabilization and motion. Of the MAPs, the tau family proteins have received special attention as they are involved in the pathophysiology of Alzheimer s disease. 

FIGURE 32-2. Treatment algorithm for Alzheimer s disease. A. Cognitive treatment. B. Treatment of psychiatric or behavioral symptoms. AD, Alzheimer s disease MMSE, Mini Mental Status Examination NINCDS-ADRDA National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer s Disease and Related Disorders Association. (From Faulkner JD, Bartlett J, Hicks P. Alzheimer s disease. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 1164, with permission.)... 

Alzheimer s disease, Parkinson disease, prion diseases (Creutzfeld-Jacob in humans, scrapie in sheep), Huntington disease, dementia with Levy s bodies, sclerosis multiplex and amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and vascular dementia are the most commonly occurring neurodegenerative diseases, with different (and often unknown) pathophysiology, creating serious health care problems and... 

Danysz W, Parsons CG, Mobius HJ, et al (2000) Neuroprotective and symptomatological action of memantine relevant for Alzheimer s disease—an unified glutamatergic hypothesis on the mechanism of action. Neurotox Res 2 85-97 Davis SM, Lees KR, Albers GW, et al (2000) Selfotel in acute ischemic stroke possible neurotoxic effects of an NMDA antagonist. Stroke 31 347-354 DeKeyser J (1991) Excitotoxic mechanisms may be involved in the pathophysiology of tardive dyskinesia. Clin Neuropharmacol 14 562-565 Del Dotto P, Pavese N, Gambaccini G, et al (2001) Intravenous amantadine improves levodopa-induced dyskinesias an acute double-blind placebo-controlled study. Mov Disord 16 515-520... 

A great number of quinoxalines fused with other heteroaromatics have been reported, especially of interest for their potential use in fighting various pathophysiological conditions like epilepsy, Parkinson s, and Alzheimer s diseases. These compounds as well as fused pyrazines are important for pharmaceutical agents, but they are excluded here since they are beyond the scope of this chapter. 

Excitotoxic activation of glutamate transmission via NMDA receptors has been postulated to contribute to the pathophysiology of Alzheimer s disease. Memantine binds to NMDA receptor channels in a use-dependent manner and produces a noncompetitive blockade. This drug appears to be better tolerated and less toxic than the cholinesterase inhibitors. Memantine is available as Namenda in 5 and 10 mg oral tablets. 

Nearly all cells express kinin receptors that mediate the activities of both bradykinin and kallidin. The activation of these G-protein coupled receptors causes relaxation of venular smooth muscle and hypotension, increased vascular permeability, contraction of smooth muscle of the gut and airway leading to increased airway resistance, stimulation of sensory neurons, alteration of ion secretion of epithelial cells, production of nitric oxide, release of cytokines from leukocytes, and the production of eicosanoids from various cell types [11,12]. Because of this broad spectrum of activity, kinins have been implicated as an important mediator in many pathophysiologies including pain, sepsis, asthma, rheumatoid arthritis, pancreatitis, and a wide variety of other inflammatory diseases. Moreover, a recent report demonstrated that bradykinin B2 receptors on the surface of human fibroblasts were upregulated three-fold beyond normal in patients with Alzheimer s disease, implicating bradykinin as a participant in the peripheral inflammatory processes associated with that disease [13]. 

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