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Topic Review
Gangliosidoses
Gangliosides are sialic acid containing complex glycolipids, anchored and enriched in the outer leaflet of neuronal plasma membranes, with their glycan chains facing the extracellular space. Undegradeable gangliosides and related glycosphingolipids and oligosaccharides accumulate progressively  in fatal lysosomal storage diseases, originally described as infantile amaurotic idiocy. Their lysosomal storage is caused by specific monogenic defects of catabolic hydrolyses or ancillary lipid-binding and -transfer proteins, essential for specific steps in their lysosomal catabolism.  However, small gangliosides can also accumulate as secondary material in other lysosomal storage diseases without a known defect in their catabolic pathway. Primary storage material of such diseases, sphingomyelin, lysosphingolipids, cholesterol and chondroitin sulfate are efficient inhibitors of specific steps of ganglioside catabolic pathway. They  can attenuate ganglioside turnover, assisted by lipid binding proteins, the GM2 activator protein (GM2AP) and saposin B
  • 972
  • 29 Oct 2020
Topic Review
Action Sports
In the last two decades, non-traditional sports activities characterized by elements such as speed, height, and exposure to natural forces knew a rapid increase in global participation. They are generally referred to as action sports (AS), with the terms adventure sports or extreme sports that could be used as interchangeable synonyms.
  • 957
  • 09 Dec 2020
Topic Review
Paroxysmal Movement Disorders
Paroxysmal movement disorders (PMDs) are rare neurological diseases typically manifesting with intermittent attacks of abnormal involuntary movements.
  • 946
  • 06 Nov 2020
Topic Review
Nrf2 and Alzheimer’s Disease
Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor that reduces oxidative stress. When reactive oxygen species (ROS) or reactive nitrogen species (RNS) are detected, Nrf2 translocates from the cytoplasm into the nucleus and binds to the antioxidant response element (ARE), which regulates the expression of antioxidant and anti-inflammatory genes. Nrf2 impairments are observed in the majority of neurodegenerative disorders, including Alzheimer’s disease (AD). The classic hallmarks of AD include β-amyloid (Aβ) plaques, and neurofibrillary tangles (NFTs). Oxidative stress is observed early in AD and is a novel therapeutic target for the treatment of AD. The nuclear translocation of Nrf2 is impaired in AD compared to controls. Increased oxidative stress is associated with impaired memory and synaptic plasticity. The administration of Nrf2 activators reverses memory and synaptic plasticity impairments in rodent models of AD. Therefore, Nrf2 activators are a potential novel therapeutic for neurodegenerative disorders including AD. 
  • 945
  • 10 Aug 2021
Topic Review
Pro-Inflammatory Molecules
Pro-inflammatory molecules, such as cytokines and chemokines, are produced in the brain by resident cells, mainly by microglia and astrocytes. Brain infiltrating immune cells constitutes another source of these molecules, contributing to an impaired neurological synapse function, affecting typical neurobehavioral and cognitive performance. Currently, there is increasing evidence supporting the notion that behavioral alterations and cognitive impairment can be associated with respiratory viral infections, such as human respiratory syncytial virus, influenza, and SARS-COV-2, which are responsible for endemic, epidemic, or pandemic outbreak mainly in the winter season.
  • 934
  • 02 Jun 2021
Topic Review
Huntington’s Disease
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by pathogenic expansions of the triplet cytosine-adenosine-guanosine (CAG) within the Huntingtin gene. These expansions lead to a prolongation of the poly-glutamine stretch at the N-terminus of Huntingtin causing protein misfolding and aggregation. Huntingtin and its pathological variants are widely expressed, but the central nervous system is mainly a ected, as proved by the wide spectrum of neurological symptoms, including behavioral anomalies, cognitive decline and motor disorders. Other hallmarks of HD are loss of body weight and muscle atrophy. This review highlights some key elements that likely provide a major contribution to muscle atrophy, namely, alteration of the transcriptional processes, mitochondrial dysfunction, which is strictly correlated to loss of energy homeostasis, inflammation, apoptosis and defects in the processes responsible for the protein quality control. The improvement of muscular symptoms has proven to slow the disease progression and extend the life span of animal models of HD, underlining the importance of a deep comprehension of the molecular mechanisms driving deterioration of muscular tissue.
  • 910
  • 24 Nov 2020
Topic Review
Human Midbrain Dopamine Neurons
Human midbrain dopamine (DA) neurons are a heterogeneous group of cells that share a common neurotransmitter phenotype and are in close anatomical proximity but display different functions, sensitivity to degeneration, and axonal innervation targets. The A9 DA neuron subtype controls motor function and is primarily degenerated in Parkinson’s disease (PD), whereas A10 neurons are largely unaffected by the condition, and their dysfunction is associated with neuropsychiatric disorders. Currently, DA neurons can only be reliably classified on the basis of topographical features, including anatomical location in the midbrain and projection targets in the forebrain.
  • 901
  • 22 Jun 2021
Topic Review
C-reactive protein (CRP) apheresis
Almost every kind of inflammation in the human body is accompanied by rising C-reactive protein (CRP) concentrations. This can include bacterial and viral infection, chronic inflammation and so-called sterile inflammation triggered by (internal) acute tissue injury. CRP is part of the ancient humoral immune response and secreted into the circulation by the liver upon respective stimuli. Its main immunological functions are the opsonization of biological particles (bacteria and dead or dying cells) for their clearance by macrophages and the activation of the classical complement pathway. This not only helps to eliminate pathogens and dead cells, which is very useful in any case, but unfortunately also to remove only slightly damaged or inactive human cells that may potentially regenerate with more CRP-free time. CRP action severely aggravates the extent of tissue damage during the acute phase response after an acute injury and therefore negatively affects clinical outcome. CRP is therefore a promising therapeutic target to rescue energy-deprived tissue either caused by ischemic injury (e.g., myocardial infarction and stroke) or by an overcompensating immune reaction occurring in acute inflammation (e.g., pancreatitis) or systemic inflammatory response syndrome (SIRS; e.g., after transplantation or surgery). Selective CRP apheresis can remove circulating CRP safely and efficiently. We explain the pathophysiological reasoning behind therapeutic CRP apheresis and summarize the broad span of indications in which its application could be beneficial with a focus on ischemic stroke as well as the results of this therapeutic approach after myocardial infarction.
  • 898
  • 17 Sep 2020
Topic Review
Therapeutic Effect of Dutasteride in Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized by the loss of upper and lower motor neurons (MNs) in the cerebral cortex, brainstem and spinal cord, with consequent weakness, atrophy and the progressive paralysis of all muscles. There is currently no medical cure, and riluzole and edaravone are the only two known approved drugs for treating this condition. However, they have limited efficacy, and hence there is a need to find new molecules. Dutasteride, a dual inhibitor of type 1 and type 2 5α-reductase (5AR) enzymes, the therapeutic purposes of which, to date, are the treatment of benign prostatic hyperplasia and androgenic alopecia, shows great anti-ALS properties by the molecular-topology methodology.
  • 878
  • 07 Sep 2022
Topic Review
Differential Diagnosis of Carpal Tunnel Syndrome
Carpal tunnel syndrome (CTS) is the most common median nerve compression neuropathy. Its symptoms and clinical presentation are well known. However, symptoms at median nerve distribution can also be caused by a proximal problem. Pronator syndrome (PS) and anterior interosseous nerve syndrome (AINS) with their typical characteristics have been thought to explain proximal median nerve problems.
  • 871
  • 27 Jul 2022
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