Promising Treatment for Alzheimer's Disease Essay

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Alzheimer’s disease (AD) is a neurodegenerative disorder(1-3) causing progressive loss of cognitive functions leading to dementia and death.(4) Older age is the highest risk factor for AD (3, 5) and the prevalence of AD rises from 3% among those 65-74years to almost 50% among those >85year(2). An estimated 5.2 million Americans of all ages had AD in 2013(1). It currently affects more than 33.9million people worldwide(4) and is predicted to be affecting more than 80million people worldwide by 2040(3) which makes treating AD a pertinent issue to be dealt with at present.
Epigenetic (defined as reversible regulation of various genome functions, occurring without change in DNA sequence)(6, 7) , modification has recently emerged as one of the
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Among them the HDACs linked to cognitive impairment in AD pathology are thought to be Class 1, HDAC 2 associated with associative and spatial memory impairment.(8) Either activating HAT or inhibiting HDAC can defend histone deacetylation but latter has proven more achievable than former(15)
HDAC inhibitors are classified into 4 main chemical families. 1. Carboxylic acids- eg Sodium butyrate, valporic acid, 4phenylbutyrate acts on Class 1 HDAC. 2. Hydroxamic acid- eg: Trichosatin, SAHA acts on Class 1 and 2 HDCA. 3. Benzamide group- eg: MS275 acts on Class 1 HDAC and 4. Cyclic tetrapeptides- Tapoxin.(15) Researches have focused mainly on class 1 and class 2 HDACi as treatment option for cognitive enhancement in AD.(21-23) The studies conducted on mouse models with AD related neurodegeneration treated by sodium butyrate(24) (Class 1 HDACi) showed rescue of cognitive functions, by acting through HDAC2 inhibition. The same models treated with SAHA, TSA (Class 2HDACi) and valporic acid (22, 23)(Class 1 HDACi) showed contextual fear and memory loss abolished.(15, 25) Also studies have shown HDACis successfully used as cognitive enhancers in invertebrates. (15)
Together these researches shows that targeting histone modifications and HDAC inhibitors can have a promising therapeutic role as cognitive enhancer in AD(11, 12, 19, 26).HDAC inhibitors are also currently researched as treatment option for many disease conditions(27-31). Epigenetics in AD can be
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