SCREENING FOR ACTIVE COMPONENTS FROM MEDICINAL PLANTS OF UTTARAKHAND TARGETING BETA SECRETASE ENZYMES IN PATHOGENESIS OF ALZHEIMERs

Abstract

Dementia can be the most common cause of disability in later life. Alzheimer s disease (AD) is most prevalent form of dementia. Current indications show that 46.8 million people are living with dementia worldwide. About 9.9 million cases of dementia have been reported in 2015 worldwide (ADI report 2015). The projection of the people living with dementia is estimated almost around double in every 20 years. The maximum numbers of people (22.9 million) are living in Asia followed by Europe, America and then Africa (with 10.5, 9.4 and 4.0 million people respectively). Economically, total estimated cost for dementia worldwide is about 818 billion US$, which will rise to 1 trillion US$ in 2018 and around 2 trillions US$ in 2030. Many pharmaceutical companies are working for development of drugs for AD treatment although several trials have failed. Several research groups are working on natural product/food supplements that can lead to prevention of AD or delay the onset of AD. The genesis of AD is due to the formation of Aand#120573; plaques and its aggregation in brain in and#120573;-secretase dependent manner. The enzymes involved in the process of Aand#946; formation have been key target for the development of the therapeutics against AD. Aand#946; aggregation depends on various factors like receptor (low-density receptor related proteins-1 (LRP1), soluble LRP1 (sLRP1) and receptor for advance glycation end product (RAGE)), enzyme degradation of Aand#946; and hormone imbalance especially estrogen in women. In addition to these factors the Aand#946; formation also occurs due to the alteration in function of secretase enzymes. The drugs developed for the cure of AD mainly confine to brain and target Aand#946; aggregation. Recent findings suggested that the formation of Aand#946; fibrils and tangles is not only localized to the central nervous system (CNS) but the alteration of blood-brain-barrier in the later stage of life allows Aand#120573;to pass through it. The plant-derived products and drugs have been accepted for treating diseases since Ayurveda period.