Search results for "neurodegeneration"

Editorial: Pathophysiologic Insights From Biomarker Studies in Neurological Disorders

2020

Oxidative stress and mitochondrial failure in the pathogenesis of glaucoma neurodegeneration

2015

This review focuses on oxidative stress and mitochondrial failure for understanding mechanisms of optic nerve damage in primary open-angle glaucoma. The chapter shows scientific evidence for the role of mitochondrial disbalance and reactive oxygen species in glaucoma neurodegeneration. Mitochondria regulate important cellular functions including reactive oxygen species generation and apoptosis. Mitochondrial alterations result from a wide variety of damaging sources. Reactive oxygen species formed by the mitochondria can act as signaling molecules, inducing lipid peroxidation and/or excitotoxicity with the result of cell lesion and death. Antioxidants may help to counteract oxidative stress…

Deregulated Splicing Is a Major Mechanism of RNA-Induced Toxicity in Huntington's Disease.

2019

Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin (HTT) gene, translating into an elongated polyglutamine stretch. In addition to the neurotoxic mutant HTT protein, the mutant CAG repeat RNA can exert toxic functions by trapping RNA-binding proteins. While few examples of proteins that aberrantly bind to mutant HTT RNA and execute abnormal function in conjunction with the CAG repeat RNA have been described, an unbiased approach to identify the interactome of mutant HTT RNA is missing. Here, we describe the analysis of proteins that preferentially bind mutant HTT RNA using a mass spectrometry approach. We show that (I) the majority of proteins captured by mutant…

Role of Adenosine Receptors in Rare Neurodegenerative Diseases with Motor Symptoms

2021

: The approval of istradefylline, an adenosine 2A receptor (A2AR) antagonist, as an addon treatment in adult patients with Parkinson’s disease by the Food and Drug Administration (FDA) and European Medicines Agency (EMA), is the latest proof of the importance of the adenosinergic system in the nervous system. Adenosine is an endogenous purine nucleoside with a role as a modulator of both neurotransmission and the inflammatory response. As such, the expression pattern of the 4 adenosine receptors (A1R, A2AR, A2BR and A3R) and the extracellular adenosine levels have attracted great interest in the pathogenesis and possible treatment of rare neurodegenerative diseases with motor symptoms. The…

Downregulation of the Astroglial Connexin Expression and Neurodegeneration after Pilocarpine-Induced Status Epilepticus

2022

Astrocytic networks and gap junctional communication mediated by connexins (Cxs) have been repeatedly implicated in seizures, epileptogenesis, and epilepsy. However, the effect of seizures on Cx expression is controversial. The present study focused on the response of Cxs to status epilepticus (SE), which is in turn an epileptogenic insult. The expression of neuronal Cx36 and astrocytic Cx30 and Cx43 mRNAs was investigated in the brain of rats in the first day after pilocarpine-induced SE. In situ hybridization revealed a progressive decrease in Cx43 and Cx30 mRNA levels, significantly marked 24 h after SE onset in neocortical areas and the hippocampus, and in most thalamic domains, whereas…

Transgenic overexpression of corticotropin releasing hormone provides partial protection against neurodegeneration in an in vivo model of acute excit…

2008

Abstract Corticotropin releasing hormone (CRH) is the central modulator of the mammalian hypothalamic–pituitary–adrenal (HPA) axis. In addition, CRH affects other processes in the brain including learning, memory, and synaptic plasticity. Moreover, CRH has been shown to play a role in nerve cell survival under apoptotic conditions and to serve as an endogenous neuroprotectant in vitro . Employing mice overexpressing murine CRH in the CNS, we observed a differential response of CRH-overexpressing mice (CRH-COE hom -Nes) to acute excitotoxic stress induced by kainate compared with controls (CRH-COE con -Nes). Interestingly, CRH-overexpression reduced the duration of epileptic seizures and pre…

The role of neuroinflammation in the pathogenesis of glaucoma neurodegeneration

2020

The chapter is a review enclosed in the volume "Glaucoma: A pancitopatia of the retina and beyond." No cure exists for glaucoma. Knowledge on the molecular and cellular alterations underlying glaucoma neurodegeneration (GL-ND) includes innovative and path-breaking research on neuroinflammation and neuroprotection. A series of events involving immune response (IR), oxidative stress and gene expression are occurring during the glaucoma course. Uveitic glaucoma (UG) is a prevalent acute/chronic complication, in the setting of chronic anterior chamber inflammation. Managing the disease requires a team approach to guarantee better results for eyes and vision. Advances in biomedicine/biotechnolog…

IN VITRO MODELS OF BLOOD-BRAIN BARRIER FORMATION AND FUNCTIONING IN MOLECULAR BASES OF NEURODEGENERETION

2005

Biodistribution of Insulin-Nanogels in Mouse: A Preliminary Study for the Treatment of Alzheimer's Disease

2017

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer's disease (AD) neurodegeneration. Thus, administration of insulin could be a strategy for AD treatment. For this aim we have designed, synthesized and characterized a nanogel system (NG) that has been conjugated to insulin molecules (NG-In) to deliver the protein into the brain, as a tool for the development of a new therapy against AD. In our preclinical study in mice, intraperitoneal injection of fluorescent-labeled NG has allowed to determine the biodistribution of NG vs time in the whole body and its clearance th…

Altered prefrontal cortex responses in older adults with subjective memory complaints and dementia during dual‐task gait : an fNIRS study

2021

People with cognitive impairments show deficits during physical performances such as gait, in particular during cognitively‐challenging conditions (i.e. dual‐task gait [DTG]). However it is unclear if people at risk of dementia, such as those with subjective memory complaints (SMC), also display gait and central deficits associated with DTG. In this study, we investigated the effects of single‐ and dual‐task gait (STG and DTG), on left prefrontal cortex (PFC) activation in elderly people with subjective memory complaints (SMC) and Dementia. 58 older adults (aged 65‐94 yrs; 26 Healthy; 23 SMC; 9 Dementia) were recruited. Gait spatiotemporal characteristics (i.e. stride velocity and length) w…