Search results for "Alzheimer"
showing 10 items of 706 documents
Regulation of Alpha-Secretase ADAM10 In vitro and In vivo: Genetic, Epigenetic, and Protein-Based Mechanisms
2017
ADAM10 (A Disintegrin and Metalloproteinase 10) has been identified as the major physiological alpha-secretase in neurons, responsible for cleaving APP in a non-amyloidogenic manner. This cleavage results in the production of a neuroprotective APP-derived fragment, APPs-alpha, and an attenuated production of neurotoxic A-beta peptides. An increase in ADAM10 activity shifts the balance of APP processing towards APPs-alpha and protects the brain from amyloid deposition and disease. Thus, increasing ADAM10 activity has been proposed an attractive target for the treatment of neurodegenerative diseases and it appears to be timely to investigate the physiological mechanisms regulating ADAM10 expr…
The Metalloprotease Meprin β Is an Alternative β-Secretase of APP
2017
The membrane bound metalloprotease meprin β is important for collagen fibril assembly in connective tissue formation and for the detachment of the intestinal mucus layer for proper barrier function. Recent proteomic studies revealed dozens of putative new substrates of meprin β, including the amyloid precursor protein (APP). It was shown that APP is cleaved by meprin β in distinct ways, either at the β-secretase site resulting in increased levels of Aβ peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments. The latter event was discussed to be rather neuroprotective, whereas the ectodomain shedding of APP by meprin β reminiscent to BACE-1 is in line with the amyloid h…
ATYPICAL CASE OF ALZHEIMER'S DISEASE MIMICKING CREUTZFELDT-JAKOB DISEASE: INTEREST OF CEREBROSPINAL FLUID BIOMARKERS IN THE DIFFERENTIAL DIAGNOSIS
2010
Effectiveness of follow-up reminiscence therapy on autobiographical memory in pathological ageing
2015
The objective is to examine the effects of reminiscence therapy (RT) on total, episodic and semantic autobiographical memory in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) groups, testing the effects of RT on different stages of autobiographical memory, and its effectiveness at follow-up. A sample composed of 43 aMCI (27 treatments, 16 controls) and 30 AD (15 treatments, 15 controls) subjects were evaluated with the Autobiographical Memory Interview (AMI) test. The RT consisted of 10 sessions lasting 60 minutes each. Both groups, aMCI and AD, showed significant effects on overall autobiographical memory; aMCI showed significant main effects on episodic and semanti…
The Role of Vitamin D as a Biomarker in Alzheimer’s Disease
2021
Vitamin D and cognition is a popular association, which led to a remarkable body of literature data in the past 50 years. The brain can synthesize, catabolize, and receive Vitamin D, which has been proved to regulate many cellular processes in neurons and microglia. Vitamin D helps synaptic plasticity and neurotransmission in dopaminergic neural circuits and exerts anti-inflammatory and neuroprotective activities within the brain by reducing the synthesis of pro-inflammatory cytokines and the oxidative stress load. Further, Vitamin D action in the brain has been related to the clearance of amyloid plaques, which represent a feature of Alzheimer Disease (AD), by the immune cell. Based on the…
Genomic structure and functional characterization of the human ADAM10 promoter
2005
The ADAM10 gene encodes a membrane-bound disintegrin-metalloproteinase, which, after overexpression in an Alzheimer disease (AD) mouse model, prevents amyloid pathology and improves long-term potentiation and memory. Because enhancing ADAM10 expression appears to be a reasonable approach for treatment of AD, we functionally analyzed the ADAM10 gene. Both human and mouse ADAM10 genes comprise approximately 160 kbp, are composed of 16 exons, and are evolutionarily highly conserved within 500 bp upstream of either translation initiation site. By using luciferase reporter assays, we demonstrate that nucleotides -2179 to -1 upstream of the human ADAM10 translation initiation site represent a fun…
Common miRNA Patterns of Alzheimer's Disease and Parkinson's Disease and Their Putative Impact on Commensal Gut Microbiota.
2019
With the rise of Next-Generation-Sequencing (NGS) methods, Micro-RNAs (miRNAs) have achieved an important position in the research landscape and have been found to present valuable diagnostic tools in various diseases such as multiple sclerosis or lung cancer. There is also emerging evidence that miRNAs play an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). Apparently, these diseases come along with changes in miRNA expression patterns which led to attempts from researchers to use these small RNA species from several body fluids for a better diagnosis and in order to observe disease progression. Additionally, it…
Funciones protectoras de los astrocitos en la inflamación y el estrés oxidativo cerebral
2018
La enfermedad de Alzheimer (EA) es una enfermedad neurodegenerativa que se presenta con mayor prevalencia en la población anciana. Afecta a alrededor de 37 millones de personas en todo el mundo. Desde el punto de vista inmunohistoquímico, la EA se caracteriza por la presencia de placas neuríticas (con el péptido tóxico Aβ1-42, entre otros) y ovillos neurofibrilares en diversas áreas del cerebro, responsables de la pérdida neuronal, el deterioro de las conexiones sinápticas y la gliosis reactiva causando la inflamación característica de esta enfermedad. Resultados previos indican que los astrocitos son células de protección para las neuronas y que podrían proteger de la inflamación y del est…
Estudio del estrés oxidativo hepático asociado a la enfermedad de Alzheimer. Efecto del tratamiento con bexaroteno y/o genisteína
2013
La enfermedad de Alzheimer (EA) no tiene una etiología perfectamente definida. Una de las teorías que se barajan como causa de la EA es la del péptido β-amiloide (βA). Esta molécula es neurotóxica y es capaz de producir estrés oxidativo. Se forma principalmente en el cerebro y se acumula formando placas extracelulares. Se ha sugerido que el βA es el eje principal de la EA, y por tanto que a partir de esta molécula se desencadenan todos los procesos asociados a la EA, lo que se ha llamado la cascada amiloidea. Otra de las hipótesis es la que la relaciona con el estrés oxidativo. Este factor sería el agente que realmente provoca toda la serie de cambios descritos en los tejidos nerviosos, a t…
Estudio de la migración neuronal de las células nerviosas de la SVZ en la enfermedad de Alzheimer
2021
En el cerebro adulto de la mayoría de los mamíferos el nicho neurogénico con mayor capacidad neurogénica es la zona ventricular-subventricular (V-SVZ). Esta región se encuentra distribuida a lo largo de las paredes de los ventrículos laterales. La capacidad neurogénica que presenta esta región se debe a la presencia de las denominadas células B. Además nos encontramos con otros tipos celulares como son las células tipo C o progenitores intermedios, las tipo A o migradoras y las tipo E o células ependimarias. Las células tipo B son capaces de dar lugar a las células tipo C que finalmente generan las células tipo A. En condiciones fisiológicas, las células tipo A migran principalmente hasta l…