Search results for "degenerative"
showing 10 items of 334 documents
Cofilin and Neurodegeneration: New Functions for an Old but Gold Protein
2021
Cofilin is an actin-binding protein that plays a major role in the regulation of actin dynamics, an essential cellular process. This protein has emerged as a crucial molecule for functions of the nervous system including motility and guidance of the neuronal growth cone, dendritic spine organization, axonal branching, and synaptic signalling. Recently, other important functions in cell biology such as apoptosis or the control of mitochondrial function have been attributed to cofilin. Moreover, novel mechanisms of cofilin function regulation have also been described. The activity of cofilin is controlled by complex regulatory mechanisms, with phosphorylation being the most important, since t…
Honey and obesity-related dysfunctions: a summary on health benefits
2020
Honey is a natural product, containing flavonoids and phenolic acids, appreciated for its therapeutic abilities since ancient times. Although the bioactive potential is linked to the composition, that is variable depending on mainly the botanical origin, honey has antioxidant and anti-inflammatory properties. Therefore, honey, administered alone or in combination with conventional therapy, might result useful in the management of chronic diseases that are commonly associated with oxidative stress and inflammation state. Obesity is a metabolic disorder characterized by visceral adiposity. The adipose tissue becomes hypertrophic and undergoes hyperplasia, resulting in a hypoxic environment, o…
The Role of the Multifunctional BAG3 Protein in Cellular Protein Quality Control and in Disease
2017
In neurons, but also in all other cells the complex proteostasis network is monitored and tightly regulated by the cellular protein quality control (PQC) system. Beyond folding of newly synthesized polypeptides and their refolding upon misfolding the PQC also manages the disposal of aberrant proteins either by the ubiquitin-proteasome machinery or by the autophagic-lysosomal system. Aggregated proteins are primarily degraded by a process termed selective macroautophagy (or aggrephagy). One such recently discovered selective macroautophagy pathway is mediated by the multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3). Under acute stress and during cellular aging, BAG3 in …
Influence of gut microbiota on neuropsychiatric disorders
2017
The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson’s dis…
Neurodegeneration in tauopathies and synucleinopathies.
2016
International audience; While increasing life expectancy is a major achievement, the global aging of societies raises a number of medical issues, such as the development of age-related disorders, including neurodegenerative diseases. The three main disease groups constituting the majority of neurodegenerative diseases are tauopathies, alpha-synucleinopathies and diseases due to repetitions of glutamine (including Huntington's disease). In each neurodegenerative disease, the accumulation of one or more aggregated proteins has been identified as the molecular signature of the disease (as seen, for example, in Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, amyotrophic lat…
Relationship Between Body Mass Index, ApoE4 Status, and PET-Based Amyloid and Neurodegeneration Markers in Amyloid-Positive Subjects with Normal Cogn…
2018
Body weight loss in late-life is known to occur at a very early stage of Alzheimer's disease (AD). Apolipoprotein E4 (ApoE4) represents a major genetic risk factor for AD and is linked to an increased cortical amyloid-β (Aβ) accumulation. Since the relationship between body weight, ApoE4, and AD pathology is poorly investigated, we aimed to evaluate whether ApoE4 allelic status modifies the association of body mass index (BMI) with markers of AD pathology. A total of 368 Aβ-positive cognitively healthy or mild cognitive impaired subjects had undergone [18F]-AV45-PET, [18F]-FDG-PET, and T1w-MRI examinations. Composite cortical [18F]-AV45 uptake and [18F]-FDG uptake in posterior cingulate cor…
Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification
2020
International audience; Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromo…
Amyotrophic lateral sclerosis modifies progenitor neural proliferation in adult classic neurogenic brain niches.
2017
Background Adult neurogenesis persists through life at least in classic neurogenic niches. Neurogenesis has been previously described as reduced in neurodegenerative diseases. There is not much knowledge about is adult neurogenesis is or not modified in amyotrophy lateral sclerosis (ALS). All previous publications has studied the ALS SOD1 (superoxide dismutase) transgenic mouse model. The purpose of this study is to examine the process of adult neurogenesis in classic niches (subventricular zone [SVZ] and subgranular zone [SGZ] of the dentate gyrus) in patients with amyotrophic lateral sclerosis (ALS), both with (ALS-FTD) and without associated frontotemporal dementia (FTD). Methods We stud…
Genetic and constitutional factors are major contributors to substantia nigra hyperechogenicity
2017
9 páginas, 2 figuras, 4 tablas
DeepWAS: Multivariate genotype-phenotype associations by directly integrating regulatory information using deep learning
2020
Genome-wide association studies (GWAS) identify genetic variants associated with traits or diseases. GWAS never directly link variants to regulatory mechanisms. Instead, the functional annotation of variants is typically inferred by post hoc analyses. A specific class of deep learning-based methods allows for the prediction of regulatory effects per variant on several cell type-specific chromatin features. We here describe “DeepWAS”, a new approach that integrates these regulatory effect predictions of single variants into a multivariate GWAS setting. Thereby, single variants associated with a trait or disease are directly coupled to their impact on a chromatin feature in a cell type. Up to…