scholarly journals Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function

2021 ◽  
Vol 22 (2) ◽  
pp. 663
Author(s):  
Alan Zanardi ◽  
Massimo Alessio

Neurodegenerative disorders can induce modifications of several proteins; one of which is ceruloplasmin (Cp), a ferroxidase enzyme found modified in the cerebrospinal fluid (CSF) of neurodegenerative diseases patients. Cp modifications are caused by the oxidation induced by the pathological environment and are usually associated with activity loss. Together with oxidation, deamidation of Cp was found in the CSF from Alzheimer’s and Parkinson’s disease patients. Protein deamidation is a process characterized by asparagine residues conversion in either aspartate or isoaspartate, depending on protein sequence/structure and cellular environment. Cp deamidation occurs at two Asparagine-Glycine-Arginine (NGR)-motifs which, once deamidated to isoAspartate-Glycine-Arginine (isoDGR), bind integrins, a family of receptors mediating cell adhesion. Therefore, on the one hand, Cp modifications lead to loss of enzymatic activity, while on the other hand, these alterations confer gain of function to Cp. In fact, deamidated Cp binds to integrins and triggers intracellular signaling on choroid plexus epithelial cells, changing cell functioning. Working in concert with the oxidative environment, Cp deamidation could reach different target cells in the brain, altering their physiology and causing detrimental effects, which might contribute to the pathological mechanism.

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.


2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.


2021 ◽  
Vol 11 (8) ◽  
pp. 3397
Author(s):  
Gustavo Assunção ◽  
Nuno Gonçalves ◽  
Paulo Menezes

Human beings have developed fantastic abilities to integrate information from various sensory sources exploring their inherent complementarity. Perceptual capabilities are therefore heightened, enabling, for instance, the well-known "cocktail party" and McGurk effects, i.e., speech disambiguation from a panoply of sound signals. This fusion ability is also key in refining the perception of sound source location, as in distinguishing whose voice is being heard in a group conversation. Furthermore, neuroscience has successfully identified the superior colliculus region in the brain as the one responsible for this modality fusion, with a handful of biological models having been proposed to approach its underlying neurophysiological process. Deriving inspiration from one of these models, this paper presents a methodology for effectively fusing correlated auditory and visual information for active speaker detection. Such an ability can have a wide range of applications, from teleconferencing systems to social robotics. The detection approach initially routes auditory and visual information through two specialized neural network structures. The resulting embeddings are fused via a novel layer based on the superior colliculus, whose topological structure emulates spatial neuron cross-mapping of unimodal perceptual fields. The validation process employed two publicly available datasets, with achieved results confirming and greatly surpassing initial expectations.


2015 ◽  
Vol 113 (9) ◽  
pp. 3159-3171 ◽  
Author(s):  
Caroline D. B. Luft ◽  
Alan Meeson ◽  
Andrew E. Welchman ◽  
Zoe Kourtzi

Learning the structure of the environment is critical for interpreting the current scene and predicting upcoming events. However, the brain mechanisms that support our ability to translate knowledge about scene statistics to sensory predictions remain largely unknown. Here we provide evidence that learning of temporal regularities shapes representations in early visual cortex that relate to our ability to predict sensory events. We tested the participants' ability to predict the orientation of a test stimulus after exposure to sequences of leftward- or rightward-oriented gratings. Using fMRI decoding, we identified brain patterns related to the observers' visual predictions rather than stimulus-driven activity. Decoding of predicted orientations following structured sequences was enhanced after training, while decoding of cued orientations following exposure to random sequences did not change. These predictive representations appear to be driven by the same large-scale neural populations that encode actual stimulus orientation and to be specific to the learned sequence structure. Thus our findings provide evidence that learning temporal structures supports our ability to predict future events by reactivating selective sensory representations as early as in primary visual cortex.


2016 ◽  
Vol 74 (8) ◽  
pp. 632-637 ◽  
Author(s):  
Vernon Furtado da Silva ◽  
Mauricio Rocha Calomeni ◽  
Rodolfo Alkmim Moreira Nunes ◽  
Carlos Elias Pimentel ◽  
Gabriela Paes Martins ◽  
...  

ABSTRACT This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.


2014 ◽  
Vol 43 (2) ◽  
pp. 218-223 ◽  
Author(s):  
Diego Blanco ◽  
José M. Vázquez ◽  
Miguel A. Rivero ◽  
Juan A. Corbera ◽  
Alberto Arencibia

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Corona Solana ◽  
Raquel Tarazona ◽  
Rafael Solana

Alzheimer’s disease (AD) represents the most common cause of dementia in the elderly. AD is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the aetiology of AD is not clear, both environmental factors and heritable predisposition may contribute to disease occurrence. In addition, inflammation and immune system alterations have been linked to AD. The prevailing hypothesis as cause of AD is the deposition in the brain of amyloid beta peptides (Aβ). Although Aβ have a role in defending the brain against infections, their accumulation promotes an inflammatory response mediated by microglia and astrocytes. The production of proinflammatory cytokines and other inflammatory mediators such as prostaglandins and complement factors favours the recruitment of peripheral immune cells further promoting neuroinflammation. Age-related inflammation and chronic infection with herpes virus such as cytomegalovirus may also contribute to inflammation in AD patients. Natural killer (NK) cells are innate lymphoid cells involved in host defence against viral infections and tumours. Once activated NK cells secrete cytokines such as IFN-γ and TNF-α and chemokines and exert cytotoxic activity against target cells. In the elderly, changes in NK cell compartment have been described which may contribute to the lower capacity of elderly individuals to respond to pathogens and tumours. Recently, the role of NK cells in the immunopathogenesis of AD is discussed. Although in AD patients the frequency of NK cells is not affected, a high NK cell response to cytokines has been described together with NK cell dysregulation of signalling pathways which is in part involved in this altered behaviour.


2017 ◽  
Vol 19 (3) ◽  
pp. 349-377
Author(s):  
Leonardo Niro Nascimento

This article first aims to demonstrate the different ways the work of the English neurologist John Hughlings Jackson influenced Freud. It argues that these can be summarized in six points. It is further argued that the framework proposed by Jackson continued to be pursued by twentieth-century neuroscientists such as Papez, MacLean and Panksepp in terms of tripartite hierarchical evolutionary models. Finally, the account presented here aims to shed light on the analogies encountered by psychodynamically oriented neuroscientists, between contemporary accounts of the anatomy and physiology of the nervous system on the one hand, and Freudian models of the mind on the other. These parallels, I will suggest, are not coincidental. They have a historical underpinning, as both accounts most likely originate from a common source: John Hughlings Jackson's tripartite evolutionary hierarchical view of the brain.


Author(s):  
Tim Palmer

It is proposed that both human creativity and human consciousness are (unintended) consequences of the human brain’s extraordinary energy efficiency. The topics of creativity and consciousness are treated separately, though have a common sub-structure. It is argued that creativity arises from a synergy between two cognitive modes of the human brain (which broadly coincide with Kahneman’s Systems 1 and 2). In the first, available energy is spread across a relatively large network of neurons. As such, the amount of energy per active neuron is so small that the operation of such neurons is susceptible to thermal (ultimately quantum decoherent) noise. In the second, available energy is focussed on a small enough subset of neurons to guarantee a deterministic operation. An illustration of how this synergy can lead to creativity with implications for computing in silicon are discussed. Starting with a discussion of the concept of free will, the notion of consciousness is defined in terms of an awareness of what are perceived to be nearby counterfactual worlds in state space. It is argued that such awareness arises from an interplay between our memories on the one hand, and quantum physical mechanisms (where, unlike in classical physics, nearby counterfactual worlds play an indispensable dynamical role) in the ion channels of neural networks. As with the brain’s susceptibility to noise, it is argued that in situations where quantum physics plays a role in the brain, it does so for reasons of energy efficiency. As an illustration of this definition of consciousness, a novel proposal is outlined as to why quantum entanglement appears so counter-intuitive.


2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Jacopo Meldolesi

AbstractLast century, neurons and glial cells were mostly believed to play distinct functions, relevant for the brain. Progressively, however, it became clear that neurons, astrocytes and microglia co-operate intensely with each other by release/binding of signaling factors, direct surface binding and generation/release of extracellular vesicles, the exosomes and ectosomes, called together vesicles in this abstract. The present review is focused on these vesicles, fundamental in various brain diseases. Their properties are extraordinary. The specificity of their membrane governs their fusion with distinct target cells, variable depending on the state and specificity of their cells of origin and target. Result of vesicle fusion is the discharge of their cargos into the cytoplasm of target cells. Cargos are composed of critical molecules, from proteins (various nature and function) to nucleotides (especially miRNAs), playing critical roles in immune and neurodegenerative diseases. Among immune diseases is multiple sclerosis, affected by extensive dysregulation of co-trafficking neural and glial vesicles, with distinct miRNAs inducing severe or reducing effects. The vesicle-dependent differences between progressive and relapsing-remitting forms of the disease are relevant for clinical developments. In Alzheimer’s disease the vesicles can affect the brain by changing their generation and inducing co-release of effective proteins, such Aβ and tau, from neurons and astrocytes. Specific miRNAs can delay the long-term development of the disease. Upon their traffic through the blood-brainbarrier, vesicles of various origin reach fluids where they are essential for the identification of biomarkers, important for diagnostic and therapeutic innovations, critical for the future of many brain patients.


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