Alzheimer's disease

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Functions of Tau gene0

Biochemical staging of tau pathology1

5-HT Receptors for the treatment of Alzheimer's Disease1

Tau Targeted Treatment Strategies in Alzheimer's Disease3

Role of Caffeine in Alzheimer's Disease5

Neurofibrillary degeneration (DNF)7

Immunotherapy Therapy for Alzheimer's Disease10

Conclusion12

CHAPTER 2: LITERATURE REVIEW

Functions of Tau gene

The TAU protein plays a critical role in the development of Alzheimer's disease, being associated with progressive neurodegeneration and loss of cognitive abilities. Thus, in Alzheimer's disease is observed hyperphosphorylation of TAU, disrupting neuron function and reducing the number of neural connections. This protein aggregation also causes the formation of neurofibrillary tangles characteristic in the brains of patients with this disease. Tau is a microtubule-associated protein that functions in normal conditions of stabilizing them. In pathological conditions are autoagrega hyperphosphorylated form filamentous structures forming diseases called tauopathies (Jin et.al, 2011, pp. 5819-5824). In this paper we have addressed the issue of assembly and aberrant phosphorylation of tau protein in their relationship with oxidative stress products 4-HNE and acrolein, discovering that acrolein induces an increase in the phosphorylation of tau to be primarily to the action of the stress-activated kinase p38, the 4-HNE acts on phosphorylated tau protein inducing the formation of polymers similar in structure to the filaments found in the tauopathy progressive supranuclear dementia (PSP). On the other hand there has been a cellular system based on Sf9 insect cells and their naturally infective vector, baculovirus for tau filament formation (Hampel et.al, 2010, pp. 30-40).

It has been shown that the presence of three mutations of tau found in the tauopathy FTDP-17 (G272V, P301L and R406W), are sufficient for the formation of tau filaments similar to those found in tauopathies, that these three mutations hyperphosphorylated tau is more than the wild tau phosphorylation and that this is mainly due to the action of GSK3 kinase. Selective inhibition of this kinase is sufficient for lithium significantly prevent the formation of these filaments (Huang, & Jiang, 2009, pp. 15-27). Finally, we have addressed the issue of regulation of the kinase GSK3, discovering that the product sodium tungstate inhibits the phosphorylation of tau at sites that require prior phosphorylation (primed), which have greater relevance to tau interaction with microtubules and that phosphorylation at these sites more inhibits the interaction between tau and tubulin phosphorylation sites not primed (Ittner, & Götz, 2010, pp. 67-72).

Biochemical staging of tau pathology

Tau pathology associated with Alzheimer's disease develops alongside a pathway that is hierarchical, sequential, invariable, and progressive. This pathway clearly illustrates the various forms of cognitive impairments that develop during these stages. Another, similar progressive mechanism of Alzheimer's disease is observed in CBD and PSP, but along other neuronal networks (Martin et.al, 2011, pp. 458-471). This process of spreading of tau pathology is stereotypical, affecting successively to ten areas of the brain, which consists of 10 stages. These stages allow to distinguish precisely, at the biochemical level, "usual" or "normal" cerebral aging from infraclinical Alzheimer's disease.

5-HT Receptors for the treatment of Alzheimer's Disease

5-HT Receptors has recently been identified as an essential drug for the attenuation of the ...