ABSTRACT
Alzheimer's disease (AD) is the main form of dementia in elderly population worldwide. By 2010 it was estimated that 35.6 million of people were living with this disease, and it was projected that this figure will triple by the year 2050. According to amyloid hypothesis, production and aggregation of amyloid beta (A-beta) peptide is the initial step in AD development. A-beta peptide is generated through proteolytic processing of amyloid precursor protein (APP); whereas its degradation depends on the action of a group of proteins collectively known as amyloiddegrading enzymes (ADE), which are reduced during aging and particularly in AD. Genetic therapy consists in the restoration of the genetic expression of a deficient protein to treat a disease. Brain restoration or overexpression of ADE reduces the levels and aggregates of A-beta, and improves learning and memory in animal models of AD. In this review we will describe the role of ADE in the regulation of A-beta levels, as well as its potential use in genetic therapy against AD.
La enfermedad de Alzheimer (EA) es la principal forma de demencia en adultos mayores a nivel mundial. En el año 2010 se estimó que 35.6 millones de personas padecen esta enfermedad y se proyectó que esta cifra se triplicará para el año 2050. De acuerdo con la hipótesis amiloide, la producción y agregación del péptido beta amiloide (A-beta) es el agente inicial en el desarrollo de la EA. El péptido A-beta se genera a partir del procesamiento proteolítico de la proteína precursora de amiloide (APP), y su degradación depende de un grupo de proteínas colectivamente conocidas como enzimas degradadoras de amiloide (EDA), las cuales se reducen durante el envejecimiento y particularmente en la EA. La terapia genética consiste en la restauración de la expresión genética de una proteína deficiente para tratar una enfermedad. La restauración o sobreexpresión cerebral de las EDA reduce los niveles y agregados de A-beta, y mejora el aprendizaje y la memoria en modelos animales de la EA. En la presente revisión se describe el papel de las EDA en la regulación de los niveles de A-beta, así como su uso potencial en la terapia genética contra la EA.
ABSTRACT
In nature, pathogenic parasite species with different susceptibility patterns of antiparasitic drugs abound. In this sense, natural products derived from plants are a potency for drugs with potential antiparasitic activity. Unfortunately, there are many metabolites and studying all of them would be costly in terms of money and resources. To this end, theoretical studies such as QSAR models could be useful. These, for the most part, predict the biological activity of the drugs against a single species of parasite. Consequently, foretell the probability with which a drug is active against many different species with a single QSAR model is an important achievement. This review consists of three parts: the first part is a review of metabolites found in nature that have antiparasitic activity, in particular the antiprotozoal (Leishmania and Trypanosoma); the second part includes a review of theoretical studies looking for a model that predicts the antiprotozoal activity of natural products; the third and final part concerns the study of theoretical models focused on the interaction between drug and receptor, analyzing new metabolites with antiprotozoal activity.
