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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
  • 1.1K
  • 29 Oct 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. 
  • 1.1K
  • 10 Aug 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.
  • 1.1K
  • 17 Sep 2020
Topic Review
Blood-Based Biomarkers in Chronic Traumatic Encephalopathy Diagnosis
Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease consistently associated with repetitive traumatic brain injuries (TBIs), which makes multiple professions, such as contact sports athletes and the military, especially susceptible to its onset. There are currently no approved biomarkers to diagnose CTE, thus it can only be confirmed through a post-mortem brain autopsy. Several imaging and cerebrospinal fluid biomarkers have shown promise in the diagnosis. However, blood-based biomarkers can be more easily obtained and quantified, increasing their clinical feasibility and potential for prophylactic use. 
  • 1.1K
  • 29 Aug 2023
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.
  • 1.1K
  • 27 Jul 2022
Topic Review
Neuropathic Pain
Neuropathic pain in humans arises as a consequence of injury or disease of somatosensory nervous system at peripheral or central level. Peripheral neuropathic pain is more common than central neuropathic pain, and is supposed to result from peripheral mechanisms, following nerve injury. The animal models of neuropathic pain show extensive functional and structural changes occurring in neuronal and non-neuronal cells in response to peripheral nerve injury. These pathological changes following damage lead to peripheral sensitization development, and subsequently to central sensitization initiation with spinal and supraspinal mechanism involved. The aim of this narrative review paper is to discuss the mechanisms engaged in peripheral neuropathic pain generation and maintenance, with special focus on the role of glial, immune, and epithelial cells in peripheral nociception. Based on the preclinical and clinical studies, interactions between neuronal and non-neuronal cells have been described, pointing out at the molecular/cellular underlying mechanisms of neuropathic pain, which might be potentially targeted by topical treatments in clinical practice. The modulation of the complex neuro-immuno-cutaneous interactions in the periphery represents a strategy for the development of new topical analgesics and their utilization in clinical settings.
  • 1.1K
  • 18 Feb 2021
Topic Review
Deep Brain Stimulation Selection Criteria
Selection criteria for deep brain stimulation (DBS) in Parkinson’s disease (PD) still rely on a document published in 1999 called ‘Core Assessment Program for Surgical Interventional Therapies in Parkinson’s Disease’. These criteria are useful in supporting the selection of candidates but could be considered both restrictive and out-of-date. Starting from the original CAPSIT-PD document, we addressed the following topics which may impact the DBS selection process: early versus delayed DBS; the evolution of the levodopa challenge test; the relevance of axial symptoms; new focus on patient-centered outcome measures; the relevance of non-motor symptoms; and a new role for genetics.
  • 1.0K
  • 09 Feb 2021
Topic Review
Visual Dysfunction in Parkinson’s Disease
Non-motor symptoms in Parkinson’s disease (PD) include ocular, visuoperceptive, and visuospatial impairments, which can occur as a result of the underlying neurodegenerative process. Ocular impairments can affect various aspects of vision and eye movement. Thus, patients can show dry eyes, blepharospasm, reduced blink rate, saccadic eye movement abnormalities, smooth pursuit deficits, and impaired voluntary and reflexive eye movements. Furthermore, visuoperceptive impairments affect the ability to perceive and recognize visual stimuli accurately, including impaired contrast sensitivity and reduced visual acuity, color discrimination, and object recognition. Visuospatial impairments are also remarkable, including difficulties perceiving and interpreting spatial relationships between objects and difficulties judging distances or navigating through the environment. Moreover, PD patients can present visuospatial attention problems, with difficulties attending to visual stimuli in a spatially organized manner. Moreover, PD patients also show perceptual disturbances affecting their ability to interpret and determine meaning from visual stimuli. And, for instance, visual hallucinations are common in PD patients.
  • 1.0K
  • 15 Aug 2023
Topic Review
Neurodegeneration with Brain Iron Accumulation
The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. However, many patients remain without a genetic diagnosis, and therefore, there must be additional yet undiscovered NBIA genes. The genetic heterogeneity and the corresponding encoded proteins emphasize that several pathways are involved in NBIA syndromes: iron and lipid metabolism, mitochondrial dynamics, and autophagy. Moreover, for these forms as well as for many neurodegenerative conditions, mitochondrial dysfunction and oxidative stress are common mechanisms of disease.
  • 1.0K
  • 22 Sep 2021
Topic Review
Epilepsy in Mitochondrial Diseases
Mitochondrial diseases are a heterogeneous group of diseases resulting from energy deficit and reduced adenosine triphosphate (ATP) production due to impaired oxidative phosphorylation. The manifestation of mitochondrial disease is usually multi-organ. Epilepsy is one of the most common manifestations of diseases resulting from mitochondrial dysfunction, especially in children.
  • 998
  • 28 Sep 2021
Topic Review
Brain Trauma, Glucocorticoids and Neuroinflammation
Brain injury is a common cause of death and disability for people of all ages worldwide. Depending on the biomechanics, brain lesions may occur both in areas of the brain directly adjacent to the place of force application and in remote areas. The mechanisms of hippocampal damage are of particular importance, since they underlie late complications of traumatic brain injury (TBI), such as epilepsy, depression and cognitive impairment. The mechanisms of reorganization of neuronal networks in the hippocampus include long-lasting chronic neuroinflammation and secondary damage to the nervous tissue. Responses and disturbances of the hypothalamic–pituitary–adrenal (HPA) axis may play a critical role in late post-traumatic pathology, in particular by modulation of synaptic activity and neuroinflammation in the hippocampus.
  • 991
  • 25 May 2022
Topic Review
Management of Poststroke Thalamic Pain
Poststroke thalamic pain (PS-TP), a type of central poststroke pain, has been challenged to improve the rehabilitation outcomes and quality of life after a stroke. It has been shown in 2.7–25% of stroke survivors; however, the treatment of PS-TP remains difficult, and in majority of them it often failed to manage the pain and hypersensitivity effectively, despite the different pharmacotherapies as well as invasive interventions. Central imbalance, central disinhibition, central sensitization, other thalamic adaptative changes, and local inflammatory responses have been considered as its possible pathogenesis. Allodynia and hyperalgesia, as well as the chronic sensitization of pain, are mainly targeted in the management of PS-TP. Commonly recommended first- and second-lines of pharmacological therapies, including traditional medications, e.g., antidepressants, anticonvulsants, opioid analgesics, and lamotrigine, were more effective than others. Nonpharmacological interventions, such as transcranial magnetic or direct current brain stimulations, vestibular caloric stimulation, epidural motor cortex stimulation, and deep brain stimulation, were effective in some cases/small-sized studies and can be recommended in the management of therapy-resistant PS-TP.
  • 982
  • 15 Jun 2022
Topic Review
Autophagy and Alzheimer’s Disease
Alzheimer’s disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated degradation of cytoplasmic constituents, which plays a critical role in maintaining cellular homeostasis. Importantly, recent studies reported that dysregulation of autophagy is associated in the pathogenesis of AD, and therefore, autophagy modulation has gained attention as a promising approach to treat AD pathogenesis. In AD, both the maturation of autolysosomes and its retrograde transports have been obstructed, which causes the accumulation of autophagic vacuoles and eventually leads to degenerating and dystrophic neurites function. However, the mechanism of autophagy modulation in APP processing and its pathogenesis have not yet been fully elucidated in AD. In the early stage of AD, APP processing and Aβ accumulation-mediated autophagy facilitate the removal of toxic protein aggregates via mTOR-dependent and -independent pathways. In addition, a number of autophagy-related genes (Atg) and APP are thought to influence the development of AD, providing a bidirectional link between autophagy and AD pathology.
  • 972
  • 28 Sep 2021
Topic Review
Seed Amplification Assays for α-Synuclein
Various disease-associated forms or strains of α-synuclein (αSynD) can spread and accumulate in a prion-like fashion during synucleinopathies such as Parkinson’s disease (PD), Lewy body dementia (DLB), and multiple system atrophy (MSA). This capacity for self-propagation has enabled the development of seed amplification assays (SAAs) that can detect αSynD in clinical samples. Notably, α-synuclein real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA) assays have evolved as ultrasensitive, specific, and relatively practical methods for detecting αSynD in a variety of biospecimens including brain tissue, CSF, skin, and olfactory mucosa from synucleinopathy patients.  
  • 972
  • 22 Apr 2022
Topic Review
Virus-Induced Neuropathogenesis
Viral infections may cause neurological disorders by directly inducing oxidative stress and interrupting immune system function, both of which contribute to neuronal death. Several reports have described the neurological manifestations in Covid-19 patients where, in severe cases of the infection, brain inflammation and encephalitis are common. Recently, extensive research-based studies have revealed and acknowledged the clinical and preventive roles of melatonin in some viral diseases. Melatonin has been shown to have antiviral properties against several viral infections which are accompanied by neurological symptoms. The beneficial properties of melatonin relate to its properties as a potent antioxidant, anti-inflammatory, and immunoregulatory molecule and its neuroprotective effects.
  • 970
  • 09 Mar 2021
Topic Review
Ion Channels of Nociception
Acute pain plays the vital role protecting our health whereas chronic and pathological pain are debilitating conditions.  However molecular mechanisms of pain which are the keys for pain relief remain largely unaddressed. Nevertheless, new molecular actors with important roles in pain mechanisms are being characterized, such as the mechanosensitive Piezo ion channels. This study presents modern trends and promising advances in the field of molecular mechanisms of pain. 
  • 969
  • 24 Mar 2021
Topic Review
Psycho-Neuro-Endocrine-Immune Basis of the Placebo Effect
The placebo effect can be defined as the improvement of symptoms in a patient after the administration of an innocuous substance in a context that induces expectations regarding its effects. During recent years, it has been discovered that the placebo response not only has neurobiological functions on analgesia, but that it is also capable of generating effects on the immune and endocrine systems. Beyond studies about its mechanism of action, the placebo effect has proved to be useful in the clinical setting with promising results in the management of neurological, psychiatric, and immunologic disorders. However, more research is needed to better characterize its potential use. 
  • 967
  • 31 May 2022
Topic Review
Alzheimer’s Disease
Many observational and clinical studies have shown that consumption of diets rich in plant polyphenols have beneficial effects on various diseases such as cancer, obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases (NDDs). Animal and cellular studies have indicated that these polyphenolic compounds contribute to such effects. The representative polyphenols are epigallocatechin-3-O-gallate in tea, chlorogenic acids in coffee, resveratrol in wine, and curcumin in curry. The results of human studies have suggested the beneficial effects of consumption of these foods on NDDs, espacially Alzheimer's disease and cellular animal experiments have provided molecular basis to indicate contribution of these representative polyphenols to these effects. This article provides updated information on the effects of these foods and their polyphenols on Alzheimer's disease with discussions on mechanistic aspects of their actions mainly based on the findings derived from basic experiments.
  • 944
  • 20 Feb 2021
Topic Review
Cerebral Ischemia
Cerebral ischemia represents the third cause of death and the first cause of disability in adults. This process results from decreasing cerebral blood flow levels as a result of the occlusion of a major cerebral artery. This restriction in blood supply generates low levels of oxygen and glucose, which leads to a decrease in the energy metabolism of the cell, producing inflammation, and finally, neurological deterioration. Currently, blood restoration of flow is the only effective approach as a therapy in terms of ischemic stroke. However, a significant number of patients still have a poor prognosis, probably owing to the increase in the generation of reactive oxygen species (ROS) during the reperfusion of damaged tissue. Oxidative stress and inflammation can be avoided by modulating mitochondrial function and have been identified as potential targets for the treatment of cerebral ischemia. In recent years, the beneficial actions of flavonoids and polyphenols against cerebrovascular diseases have been extensively investigated. The use of resveratrol (RSV) has been shown to markedly decrease brain damage caused by ischemia in numerous studies. According to in vitro and in vivo experiments, there is growing evidence that RSV is involved in several pathways, including cAMP/AMPK/SIRT1 regulation, JAK/ERK/STAT signaling pathway modulation, TLR4 signal transduction regulation, gut/brain axis modulation, GLUT3 up-regulation inhibition, neuronal autophagy activation, and de novo SUR1 expression inhibition.
  • 942
  • 09 Sep 2021
Topic Review
Gender Differences in Parkinson’s Disease
Parkinson’s disease (PD) is a debilitating neurodegenerative disease that is responsible for cognitive impairment, non-motor, and motor symptoms, which has been found to significantly affect health-related quality of life (HRQoL). The gender differences of the health-related quality of life of subjects with Parkinson’s disease have been observed in a number of studies.
  • 940
  • 04 Jun 2021
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