Search results for "neurodegeneration"
showing 10 items of 268 documents
From obesity to Alzheimer's disease through insulin resistance
2021
Alzheimer's disease is one of the most frequent forms of dementia. It is a progressive neurodegenerative disease, characterized by presence of amyloid plaques and neurofibrillary tangles in the brain. Obesity is regarded as abnormal fat accumulation with deleterious impact on human health. There is full scientific evidence that obesity and the metabolic comorbidities (e.g., insulin resistance, hyperglycaemia, and type 2 diabetes) are related to Alzheimer's disease and likely in the causative pathway. Numerous studies have identified several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammation. In this review, we present how obesit…
A new window in multiple sclerosis pathology: non-conventional quantitative magnetic resonance imaging outcomes
2010
Recent findings suggest that neuronal pathology occurs early in the course of multiple sclerosis and seems to be responsible for accumulation of disability. Nonetheless, the nervous system has an intrinsic potential for repair and compensation in the neuronal component. Disease-modifying drugs such as glatiramer acetate interfere with, and down-regulate, inflammatory pathology and slow neurodegeneration. Moreover, certain regulatory cytokines and neurotrophic factors have the capacity to promote neuronal and axonal repair. Given the importance of neuronal injury in multiple sclerosis and the potential of certain treatments for neuronal repair, it is important to possess adequate and sensiti…
The HIF1α-PFKFB3 Pathway: A Key Player in Diabetic Retinopathy
2021
Abstract Diabetic retinopathy (DR) is the leading cause of blindness for adults in developed countries. Both microvasculopathy and neurodegeneration are implicated in mechanisms of DR development, with neuronal impairment preceding microvascular abnormalities, which is often underappreciated in the clinic. Most current therapeutic strategies, including anti-vascular endothelial growth factor (anti-VEGF)-antibodies, aim at treating the advanced stages (diabetic macular edema and proliferative diabetic retinopathy) and fail to target the neuronal deterioration. Hence, new therapeutic approach(es) intended to address both vascular and neuronal impairment are urgently needed. The hypoxia-induci…
Sestrins: Novel antioxidant and AMPK-modulating functions regulated by exercise?
2013
Oxidative stress results from damage to tissues caused by free radicals and is increased by exercise. Peroxiredoxins (PRXs) maintain the cellular reducing environment by scavenging intracellular hydrogen peroxide. It has been recently noted that physical exercise has a positive effect on the PRX system, exerting a protective effect against oxidative stress-induced damage. However, other compounds, such as sestrins (SESNs), a stress-inducible protein family with antioxidant properties, should also be considered in the function of PRXs. SESNs are clearly involved in the regeneration process of PRXs and therefore may also be modulated by physical exercise. In addition, SESNs are clearly involv…
Substance P Saliva Reduction Predicts Pharyngeal Dysphagia in Parkinson's Disease
2019
Introduction: Although patients with Parkinson's disease (PD) often suffer from oropharyngeal dysphagia, knowledge about the underlying pathophysiological mechanisms is limited. Substance P (SP) is a localization-independent neurotransmitter of the entire nervous system. Reduced levels of SP were found in saliva of patients with impaired cough reflex and in advanced stages of PD. The aim of the study was to investigate SP in PD patients in order to gain further insights into the underlying pathophysiology of PD-related dysphagia and to evaluate the potential of SP as a biomarker for early dysphagia. Methods: Flexible endoscopic evaluation of swallowing (FEES) was used to objectively assess …
Selected peptides targeted to the NMDA receptor channel protect neurons from excitotoxic death
1998
Excitotoxic neuronal death, associated with neurodegeneration and stroke, is triggered primarily by massive Ca2+ influx arising from overactivation of glutamate receptor channels of the N-methyl-D-aspartate (NMDA) subtype. To search for channel blockers, synthetic combinatorial libraries were assayed for block of agonist-evoked currents by the human NR1-NR2A NMDA receptor subunits expressed in amphibian oocytes. A set of arginine-rich hexapeptides selectively blocked the NMDA receptor channel with IC50 approximately 100 nM, a potency similar to clinically tolerated blockers such as memantine, and only marginally blocked on non-NMDA glutamate receptors. These peptides prevent neuronal cell d…
Poor Bone Quality in Patients With Amyotrophic Lateral Sclerosis
2020
Objective: Musculoskeletal functional deterioration in Amyotrophic lateral sclerosis (ALS) is associated with an increase in bone fractures. The purpose of this study was to evaluate the influence of sex, ALS type, on bone quality in patients with ALS compared to healthy controls. The impact on bone health of the clinical status and some metabolic parameters was also analyzed in ALS patients.Methods: A series of 33 voluntary patients with ALS, and 66 healthy individuals matched in sex and age underwent assessment of bone mass quality using quantitative ultrasound (QUS) of the calcaneus. Ultrasonic broadband attenuation (BUA), the speed of sound (SOS), stiffness index and T-score were measur…
Effet neuroprotecteur de l’accident ischémique transitoire
2011
Transient ischemic attack (TIA) is a well-recognized risk factor of ischemic stroke. Hence, 7 to 25% of ischemic stroke patients have a history of TIA, and the risk of ischemic stroke after TIA is about 15% at 3 months. However, epidemiological studies have demonstrated that among patients with ischemic stroke, those with a history of TIA have better functional and vital prognoses. This protective effect is particularly found in case of recent and short TIA, and in case of non-lacunar ischemic stroke. Hence, TIA can induce endogenous neuroprotection by the ischemic tolerance phenomenon that decreases the neurodegeneration usually caused by a severe cerebral ischemia in a non-preconditioned …
Potential Involvement of Impaired Venous Outflow from the Brain in Neurodegeneration: Lessons Learned from the Research on Chronic Cerebrospinal Veno…
2019
About 10 years ago, the so-called chronic cerebrospinal venous insufficiency syndrome was discovered. This clinical entity, which is associated with extracranial venous abnormalities that impair venous outflow from the brain, was initially found exclusively in multiple sclerosis patients. Currently, we know that such venous lesions can also be revealed in other neurological pathologies, including Alzheimer’s and Parkinson’s diseases. Although direct causative role of chronic cerebrospinal venous insufficiency in these neurological diseases still remains elusive, in this paper, we suggest that perhaps an abnormal venous drainage of the brain affects functioning of the glymphatic system, whi…
Metalloprotease meprin beta generates nontoxic N-terminal amyloid precursor protein fragments in vivo.
2011
Identification of physiologically relevant substrates is still the most challenging part in protease research for understanding the biological activity of these enzymes. The zinc-dependent metalloprotease meprin β is known to be expressed in many tissues with functions in health and disease. Here, we demonstrate unique interactions between meprin β and the amyloid precursor protein (APP). Although APP is intensively studied as a ubiquitously expressed cell surface protein, which is involved in Alzheimer disease, its precise physiological role and relevance remain elusive. Based on a novel proteomics technique termed terminal amine isotopic labeling of substrates (TAILS), APP was identified …