Search results for "HEI"
showing 10 items of 2846 documents
Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance
2017
International audience; Chronic low-grade inflammation during aging (inflammaging) is associated with cognitive decline and neurodegeneration; however, the mechanisms underlying inflammaging are unclear. We studied a population (n = 361) of healthy young and old adults from the MyoAge cohort. Peripheral levels of C-X-C motif chemokine ligand 10 (CXCL10) was found to be higher in older adults, compared with young, and negatively associated with working memory performance. This coincided with an age-related reduction in blood DNA methylation at specific CpGs within the CXCL10 gene promoter. In vitro analysis supported the role of DNA methylation in regulating CXCL10 transcription. A polymorph…
Heat Shock Proteins in Alzheimer’s Disease: Role and Targeting
2018
Among diseases whose cure is still far from being discovered, Alzheimer’s disease (AD) has been recognized as a crucial medical and social problem. A major issue in AD research is represented by the complexity of involved biochemical pathways, including the nature of protein misfolding, which results in the production of toxic species. Considering the involvement of (mis)folding processes in AD aetiology, targeting molecular chaperones represents a promising therapeutic perspective. This review analyses the connection between AD and molecular chaperones, with particular attention toward the most important heat shock proteins (HSPs) as representative components of the human chaperome: Hsp60,…
Alzheimer's disease: Only prevention makes sense
2018
Alzheimer's disease therapeutics is one of the most important endeavours in today's clinical investigation. Over more than 30 years of research, no disease-modifying treatment has been approved by either the FDA or the EMA to treat Alzheimer's disease. Recently, the evidence of pathological alterations in the brain tissue has been gathered showing that the signs of brain damage appear more than 20 years before the onset of Alzheimer's dementia. The major aim of this review is to underpin the idea that in Alzheimer's therapeutics, only prevention makes sense. It is difficult to visualise that would-be patients may be treated with endovenous administration of antibodies for several years to d…
Early increased density of cyclooxygenase-2 (COX-2) immunoreactive neurons in Down syndrome
2017
iNeuroinflammation is one of the hallmarks of Alzheimer's disease. One of the enzymes involved in neuroinflammation, even in early stages of the disease, is COX-2, an inducible cyclooxygenase responsible for the generation of eicosanoids and for the generation of free radicals. Individuals with Down syndrome develop Alzheimer's disease early in life. Previous studies pointed to the possible overexpression of COX-2 and correlated it to brain regions affected by the disease. We analysed the COX-2 expression levels in individuals with Down syndrome and in young, adult and old mice of the Ts65Dn mouse model for Down syndrome. We have observed an overexpression of COX-2 in both, Down syndrome in…
Olesoxime improves cerebral mitochondrial dysfunction and enhances Aβ levels in preclinical models of Alzheimer's disease.
2019
Abstract Background Approved drugs for Alzheimer's disease (AD) only have a symptomatic effects and do not intervene causally in the course of the disease. Olesoxime (TRO19622) has been tested in AD disease models characterized by improved amyloid precursor protein processing (AβPP) and mitochondrial dysfunction. Methods Three months old Thy-1-AβPPSL (tg) and wild type mice (wt) received TRO19622 (100 mg/kg b.w.) in supplemented food pellets for 15 weeks (tg TRO19622). Mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels were determined in dissociated brain cells (DBC). Respiration was analyzed in mitochondria isolated from brain tissue. Citrate synthase (CS) activ…
When Does Alzheimer′s Disease Really Start? The Role of Biomarkers
2021
While Alzheimer’s disease (AD) classical diagnostic criteria rely on clinical data from a stablished symptomatic disease, newer criteria aim to identify the disease in its earlier stages. For that, they incorporated the use of AD’s specific biomarkers to reach a diagnosis, including the identification of Aβ and tau depositions, glucose hypometabolism, and cerebral atrophy. These biomarkers created a new concept of the disease, in which AD’s main pathological processes have already taken place decades before we can clinically diagnose the first symptoms. Therefore, AD is now considered a dynamic disease with a gradual progression, and dementia is its final stage. With …
The MID1 protein is a central player during development and in disease.
2015
Loss-of-function mutations in the MID1 gene cause a rare monogenic disorder, Opitz BBB/G syndrome (OS), which is characterized by malformations of the ventral midline. The MID1 gene encodes the MID1 protein, which assembles a large microtubule-associated protein complex. Intensive research over the past several years has shed light on the function of the MID1 protein as a ubiquitin ligase and regulator of mTOR signalling and translational activator. As a central player in the cell MID1 has been implicated in the pathogenesis of various other disorders in addition to OS including cancer and neurodegenerative diseases. Influencing the activity of the MID1 protein complex is a promising new st…
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…
Menstrual dysfunction and body weight dissatisfaction among Finnish young athletes and non-athletes.
2020
To determine the prevalence of menstrual dysfunction (MD; i.e. oligomenorrhea or amenorrhea) and attitudes towards body weight among athletes and non‐athletes, we studied a cohort of athletes and non‐athletes, in adolescence (14–16 years) and subsequently in young adulthood (18–20 years). We further studied the differences between athletes reporting MD and eumenorrheic athletes at both time periods and identified physical and behavioural characteristicsthat might predict MD in young adulthood. Data were collected using questionnaires, accelerometers, and a pre‐participation screening. In adolescence, the athletes reported current primary amenorrhea more often than the non‐athletes (4.7% vs.…