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
BACKGROUND: Psoriasis is a chronic skin disease that is probably a T cell-mediated autoimmune condition which is strongly associated with streptococcal throat infections. Although some groups have associated the involved response with different streptococcal antigens, M protein has been described as the major virulence factor of Streptococcus pyogenes. Thus, it is necessary to describe some features of the cellular responses to this streptococcal antigen. METHODS: Proliferation and Th1/Th2 cytokine production of peripheral blood mononuclear cells (PBMC) in response to total soluble extracts from type M5 S. pyogenes with (TSE37Sp) and without (M(-)TSESp) M protein were analyzed in 10 psoriatic patients and 10 healthy controls. RESULTS: PBMC from both patients and controls proliferated to both extracts. Responses to M(-)TSESp were significantly lower than those to TSE37Sp (P < 0.05). PBMC IL-2 and gammaIFN production after TSE37Sp stimulus was much higher than after M(-)TSESp antigenic stimulation in both groups (P < 0.05). Meanwhile, IL-4 production was quite low in both groups and in response to both extracts. We found a differential production of IL-10 between groups. PBMC from healthy controls responded to TSE37Sp with a much higher production of this cytokine as compared to the responses showed to M(-)TSESp while the cells from psoriatic patients responded without differences in the production of IL-10. CONCLUSION: Results obtained suggest an important Th1 response to M protein in psoriatic patients which could be associated with the cellular responses involved in psoriasis, while healthy subjects respond in a probably non-Th2 IL-10 producing regulatory T cells fashion.
