Implicación de la síntesis de nucleótidos de pirimidina en la enfermedad de Alzheimer

Pese a que las neuronas son células completamente diferenciadas, sus requerimientos de pirimidinas para producir y mantener la extensa membrana plasmática que compone sus neuritas hacen suponer que la ruta de síntesis de novo de nucleótidos de pirimidina necesita estar activa en el cerebro humano adulto. Esta ruta está conectada con el sistema de fosforilación oxidativa (OXPHOS) a través de la enzima DHODH. Muchos pacientes con enfermedad de Alzheimer (AD) muestran una disfunción OXPHOS muy temprana. Así, los individuos con AD podrían, por tanto, tener afectada la síntesis de nucleótidos de pirimidina y la ruta de salvamento de pirimidinas sería particularmente importante para ellos. Con este trabajo hemos confirmado no solo que la ruta de síntesis de novo de nucleótidos de pirimidina se encuentra en cerebro humano adulto, sino que tanto esta ruta como la de salvamento de pirimidinas están afectadas en los pacientes con AD. Además, usando un modelo celular, hemos confirmado como la disfunción OXPHOS, reduciendo secundariamente la actividad de la ruta de síntesis de novo de nucleótidos de pirimidina, provoca alteraciones en distintas funciones neuronales, que son corregidas por la administración de uridina.La disminución en la actividad de las rutas de síntesis de nucleótidos de pirimidina parece ser un mecanismo fisiopatológico de la AD, secundario a la disfunción OXPHOS, que podría tratarse mediante la administración de uridina.<br /

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

The Spanish version of Face-Name Associative Memory Exam (S-FNAME) performance is related to amyloid burden in Subjective Cognitive Decline

The Face-Name Associative Memory Exam (FNAME) is a paired associative memory test created to detect memory deficits in individuals with preclinical Alzheimer’s disease (AD). Worse performance on FNAME in cognitively healthy individuals were found related to higher amyloid beta (Aβ) burden measured with Positron-Emission-Tomography using 11C-PiB (PiB-PET). We previously reported normative data of a Spanish version of FNAME (S-FNAME) in cognitively healthy Spanish-speaking subjects. The aim of the present study was to determine whether performance on S-FNAME was associated with Aβ burden in subjective cognitive decline (SCD) individuals. 200 SCD subjects received neurological and neuropsychological assessments, including the S-FNAME and the Word List task from the Wechsler-Memory-Scale-III (WMS-III). Moreover, they received an MRI and (18)F-Florbetaben Positron-Emission-Tomography (FBB-PET) to measure Aβ burden. Three cognitive factor composites were derived for the episodic memory measures (face-name [SFN-N], face-occupation [SFN-O] and WMS-III) to determine whether episodic memory performance was related to Aβ deposition. Higher global Aβ deposition was significantly related to worse performance on SFN-N but not with SFN-O or WMS-III Composite. Moreover, worse SFN-N performance was significantly related to higher Aβ deposition in bilateral Posterior Cingulate Cortex. The S-FNAME may be a promising neuropsychological tool for detecting SCD individuals with preclinical AD