Search results for "Neurodegenerative disorders"
showing 10 items of 17 documents
Oxidative Stress, a Crossroad Between Rare Diseases and Neurodegeneration
2020
Oxidative stress is an imbalance between production and accumulation of oxygen reactive species and/or reactive nitrogen species in cells and tissues, and the capacity of detoxifying these products, using enzymatic and non-enzymatic components, such as glutathione. Oxidative stress plays roles in several pathological processes in the nervous system, such as neurotoxicity, neuroinflammation, ischemic stroke, and neurodegeneration. The concepts of oxidative stress and rare diseases were formulated in the eighties, and since then, the link between them has not stopped growing. The present review aims to expand knowledge in the pathological processes associated with oxidative stress underlying …
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 …
Neurodegenerative diseases: Might citrus flavonoids play a protective role?
2016
Neurodegenerative diseases (ND) result from the gradual and progressive degeneration of the structure and function of the central nervous system or the peripheral nervous system or both. They are characterized by deterioration of neurons and/or myelin sheath, disruption of sensory information transmission and loss of movement control. There is no effective treatment for ND, and the drugs currently marketed are symptom-oriented, albeit with several side effects. Within the past decades, several natural remedies have gained attention as potential neuroprotective drugs. Moreover, an increasing number of studies have suggested that dietary intake of vegetables and fruits can prevent or delay th…
Transcriptomic and Genetic Associations between Alzheimer's Disease, Parkinson's Disease, and Cancer.
2021
Simple Summary Epidemiological studies have identified a link between neurodegenerative disorders and a reduced risk of overall cancer. Increases and decreases in the risk of site-specific cancers have also been reported. However, it is still unknown whether these associations arise due to shared genetic and molecular factors or are explained by other phenomena (e.g., biases in epidemiological studies or the use of medication). In this study, we aimed to investigate the potential molecular, genetic, and pharmacological links between Alzheimer’s and Parkinson’s diseases and a large panel of 22 cancer types. To examine the overlapping involvement of genes and pathways, we obtained differentia…
Emerging Roles of RNA 3′-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders
2020
A crucial feature of gene expression involves RNA processing to produce 3′ ends through a process termed 3′ end cleavage and polyadenylation (CPA). This ensures the nascent RNA molecule can exit the nucleus and be translated to ultimately give rise to a protein which can execute a function. Further, alternative polyadenylation (APA) can produce distinct transcript isoforms, profoundly expanding the complexity of the transcriptome. CPA is carried out by multi-component protein complexes interacting with multiple RNA motifs and is tightly coupled to transcription, other steps of RNA processing, and even epigenetic modifications. CPA and APA contribute to the maintenance of a multitude of dive…
A Brief Overview on BDNF-Trk Pathway in the Nervous System: A Potential Biomarker or Possible Target in Treatment of Multiple Sclerosis?
2022
The growing incidence of neurodegenerative disorders in our populations is leading the research to identify potential biomarkers and targets for facilitating their early management and treatments. Biomarkers represent the crucial indicators of both physiological and pathological processes. Specific changes in molecular and cellular mechanisms of physiological processes result in biochemical alterations at systemic level, which can give us comprehensive information regarding the nature of any disease. In addition, any disease biomarker should be specific and reliable, able to consent of distinguishing the physiological condition of a tissue, organ, or system from disease, and be diverse amon…
Oleic Derivatives of Dopamine and Respiration
2018
Ventilatory inhibition is considered an undesirable pharmacological side effect of pharmacotherapy in neurodegenerative conditions underlain by brain dopamine deficiency. In this context, oleic derivatives of dopamine or N-acyl-dopamines are novel substances that may be of high therapeutic interest as having the ability to cross the blood-brain barrier and acting in dopamine-like manner. In the present study we seek to define the influence of N-acyl-dopamines on lung ventilation and its hypoxic responses in the rat. We found that N-oleoyl-dopamine decreased both normoxic and peak hypoxic ventilation in response to 8% acute hypoxia, on average, by 31% and 41%, respectively. Its metabolite, 3…
Exploring by whole exome sequencing patients with initial diagnosis of Rubinstein-Taybi syndrome: the interconnections of epigenetic machinery disord…
2019
Rubinstein–Taybi syndrome (RSTS) is an autosomal-dominant neurodevelopmental disease affecting 1:125,000 newborns characterized by intellectual disability, growth retardation, facial dysmorphisms and skeletal abnormalities. RSTS is caused by mutations in genes encoding for writers of the epigenetic machinery: CREBBP (~ 60%) or its homologous EP300 (~ 10%). No causative mutation is identified in up to 30% of patients. We performed whole-exome sequencing (WES) on eight RSTS-like individuals who had normal high-resolution array CGH testing and were CREBBP- and EP300-mutation -negative, to identify the molecular cause. In four cases, we identified putatively causal variants in three genes (ASXL…
Sleep quality in caregivers of patients with Alzheimer’s disease and Parkinson’s disease and its relationship to quality of life
2012
ABSTRACTBackground: Knowledge about sleep complaints of caregivers of patients with Alzheimer's disease (AD) and Parkinson's disease (PD) is limited, and we lack information about the relationship between caregivers’ sleep problems and their quality of life (QoL).Methods: We evaluated subjective sleep quality and its relationship to QoL in a group of 80 caregivers of patients with AD (ADCG, n = 40) and PD (PDCG, n = 40), and in 150 controls. Information about night-time complaints was collected using the Pittsburgh Sleep Quality Index (PSQI). QoL was measured using the McGill QoL Questionnaire.Results: Eighteen ADCG (45%), 22 PDCG (55%), and 45 (30%) controls reported poor sleep quality. Me…
Neurodegenerative disorders: from molecules to man (part 1)
2007
Neurons are typically post-mitotic cells. This means that they are expected to have a life span comparable to that of their carriers. Unfortunately, sometimes, they die prematurely as a result of complex processes known as “neurodegeneration”. Neurodegenerative diseases are now generally considered a group of disorders that seriously and progressively impair the functions of the nervous system through causing the selective neuronal vulnerability of specific brain regions. Neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer Disease (AD), Multiple Sclerosis (MS), and prion disease represent several distinct categories of disease and each manifests its own unique symptoms. …