Search results for "degenerative diseases"
showing 10 items of 158 documents
Fractal analyses reveal independent complexity and predictability of gait
2017
Locomotion is a natural task that has been assessed since decades and used as a proxy to highlight impairments of various origins. Most studies adopted classical linear analyses of spatio-temporal gait parameters. Here, we use more advanced, yet not less practical, non-linear techniques to analyse gait time series of healthy subjects. We aimed at finding more sensitive indexes related to spatio-temporal gait parameters than those previously used, with the hope to better identify abnormal locomotion. We analysed large-scale stride interval time series and mean step width in 34 participants while altering walking direction (forward vs. backward walking) and with or without galvanic vestibular…
The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis.
2005
G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute stroke. G-CSF displays strong anti-apoptotic activity in mature neurons and activates multiple cell survival pathways. Both G-CSF and its receptor are widely expressed by neurons in the CNS, and their expression is induced by ischemia, which suggests an autocrine protective signaling mechanism. Surprisingly, the G-CSF receptor was also expressed by adult neural stem cells, and G-CSF induced neurona…
High-yield Production of Amyloid-β Peptide Enabled by a Customized Spider Silk Domain
2020
AbstractDuring storage in the silk gland, the N-terminal domain (NT) of spider silk proteins (spidroins) keeps the aggregation-prone repetitive region in solution at extreme concentrations. We observe that NTs from different spidroins have co-evolved with their respective repeat region, and now use an NT that is distantly related to previously used NTs, for efficient recombinant production of the amyloid-β peptide (Aβ) implicated in Alzheimer’s disease. A designed variant of NT from Nephila clavipes flagelliform spidroin, which in nature allows production and storage of β-hairpin repeat segments, gives exceptionally high yields of different human Aβ variants as a solubility tag. This tool e…
Molecular topology as novel strategy for discovery of drugs with aβ lowering and anti-aggregation dual activities for Alzheimer's disease.
2014
Background and Purpose: In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy. Experimental Approach: We used MT to include multiple bioactive properties that allows for the identification of multifunctional single agent compounds, in this case, the dual func…
Neurodegeneration in multiple sclerosis: novel treatment strategies.
2012
In recent years it has become clear that the neuronal compartment already plays an important role early in the pathology of multiple sclerosis (MS). Neuronal injury in the course of chronic neuroinflammation is a key factor in determining long-term disability in patients. Viewing MS as both inflammatory and neurodegenerative has major implications for therapy, with CNS protection and repair needed in addition to controlling inflammation. Here, the authors' review recently elucidated molecular insights into inflammatory neuronal/axonal pathology in MS and discuss the resulting options regarding neuroprotective and regenerative treatment strategies.
Beta-amyloid monomers are neuroprotective
2009
The 42-aa-long β-amyloid protein—Aβ1-42—is thought to play a central role in the pathogenesis of Alzheimer's disease (AD) (Walsh and Selkoe, 2007). Data from AD brain (Shankar et al., 2008), transgenic APP (amyloid precursor protein)-overexpressing mice (Lesné et al., 2006), and neuronal cultures treated with synthetic Aβ peptides (Lambert et al., 1998) indicate that self-association of Aβ1-42monomers into soluble oligomers is required for neurotoxicity. The function of monomeric Aβ1-42is unknown. The evidence that Aβ1-42is present in the brain and CSF of normal individuals suggests that the peptide is physiologically active (Shoji, 2002). Here we show that synthetic Aβ1-42monomers support …
Neurons as targets for T cells in the nervous system
2013
International audience; Accumulating evidence shows that T cells penetrate the central nervous system (CNS) parenchyma in several autoimmune, infectious, and degenerative neurological diseases. The structural and functional consequences for CNS neurons of their encounter with activated T cells have been investigated in several experimental systems, including ex vivo co-cultures, electrophysiology, and in vivo imaging. Here, we review the modalities of neuron/T cell interactions. We substantiate the contention that T cells are directly responsible for neuronal damage in a large number of neurological diseases and discuss mechanisms of neuronal damage mediated by distinct T cell subsets, the …
Extracellular Vesicle-Mediated Cell–Cell Communication in the Nervous System: Focus on Neurological Diseases
2019
Extracellular vesicles (EVs), including exosomes, are membranous particles released by cells into the extracellular space. They are involved in cell differentiation, tissue homeostasis, and organ remodelling in virtually all tissues, including the central nervous system (CNS). They are secreted by a range of cell types and via blood reaching other cells whose functioning they can modify because they transport and deliver active molecules, such as proteins of various types and functions, lipids, DNA, and miRNAs. Since they are relatively easy to isolate, exosomes can be characterized, and their composition elucidated and manipulated by bioengineering techniques. Consequently, exosomes appear…
Emerging roles of extracellular vesicles in the nervous system.
2014
Information exchange executed by extracellular vesicles, including exosomes, is a newly described form of intercellular communication important in the development and physiology of neural systems. These vesicles can be released from cells, are packed with information including signaling proteins and both coding and regulatory RNAs, and can be taken up by target cells, thereby facilitating the transfer of multilevel information. Recent studies demonstrate their critical role in physiological processes, including nerve regeneration, synaptic function, and behavior. These vesicles also have a sinister role in the propagation of toxic amyloid proteins in neurodegenerative conditions, including …
Knowledge and Attitudes towards Palliative Care : Validation of the Spanish Version of Questionnaire on Palliative Care for Advanced Dementia
2022
Background: Palliative care is essential in the care of people with advanced dementia, due to the increasing number of patients requiring care in the final stages of life. Nurses need to acquire specific knowledge and skills to provide quality palliative care. The Questionnaire on Palliative Care for Advanced Dementia (qPAD) is useful for assessing knowledge and attitudes toward palliative care, but its adaptation to the Spanish language and analysis of its effectiveness and usefulness for the Spanish culture is lacking. Objective: To report on the Spanish language adaptation and psychometric analysis of the qPAD. Methods: The Questionnaire on Palliative Care for Advanced Dementia Spanish v…