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Topic Review
Focal Cortical Dysplasia in Tuberous Sclerosis Complex
Patients with tuberous sclerosis complex present with cognitive, behavioral, and psychiatric impairments, such as intellectual disabilities, autism spectrum disorders, and drug-resistant epilepsy. It has been shown that these disorders are associated with the presence of cortical tubers. Tuberous sclerosis complex results from inactivating mutations in the TSC1 or TSC2 genes, resulting in hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway, which regulates cell growth, proliferation, survival, and autophagy. TSC1 and TSC2 are classified as tumor suppressor genes and function according to Knudson’s two-hit hypothesis, which requires both alleles to be damaged for tumor formation. However, a second-hit mutation is a rare event in cortical tubers. This suggests that the molecular mechanism of cortical tuber formation may be more complicated and requires further research.
  • 884
  • 25 Jun 2023
Topic Review
Fabry Disease and Central Nervous System Involvement
Fabry disease (FD; MIM: 301500) is a lysosomal storage disorder (LSD) with an X-linked inheritance secondary to mutations in the GLA gene (NCBI: NC_000023.11; Xq22), which results in the absent or decreased activity of lysosomal hydrolase α-galactosidase A (AGA, α-GalA; BRENDA: EC3.2.1.22). The consequent accumulation of its primary substrate globotriaosylceramide (Gb3) and its derivatives (mainly globotriaosylsphingosine (lyso-Gb3)) results in injury to multiple organs and systemic dysfunction, with endothelial vascular involvement being the main pathological alteration in the disease. Although FD is among the most prevalent lysosomal disorders, with up to 2.5 cases per 100,000 males, little is known or has been reported regarding the involvement of the central nervous system (CNS) beyond cerebrovascular disease. This is particularly striking since there are studies available relating FD to certain neuropsychological profiles, Parkinson’s disease (PD), the accumulation of Lewy bodies, and movement or psychiatric disorders.
  • 884
  • 20 Mar 2023
Topic Review
Circulating Cytokines and Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that has no effective treatment. The lack of any specific biomarker that can help in the diagnosis or prognosis of ALS has made the identification of biomarkers an urgent challenge. Multiple panels have shown alterations in levels of numerous cytokines in ALS, supporting the contribution of neuroinflammation to the progressive motor neuron loss. 
  • 883
  • 10 Jan 2022
Topic Review
Functional Neurological Symptom Disorder
A functional neurological disorder (FND) is a condition in which patients experience neurological symptoms such as weakness, movement disorders, sensory symptoms and blackouts. In the past, the brain of a patient with functional neurological symptom disorder was believed to be structurally normal, but functioning incorrectly. Patients with FND were marginalized for much of the 20th century, with limited clinical and neuroscientific interest. Converging evidence from several studies using different techniques and paradigms has now demonstrated distinctive brain activation patterns associated with functional deficits, unlike those seen in actors simulating similar deficits.  New research has uncovered pathways in the brain’s white matter that may be altered in patients with functional neurological disorder (FND). The new findings advance current understanding of the mechanisms involved in this disease, and offer the possibility of identifying markers of the condition and patients’ prognosis. Historically, other terms have been used to describe these symptoms. Symptoms of functional neurological disorders are clinically recognisable, but are not categorically associated with a definable organic disease. The intended contrast is with an organic brain syndrome, although the terms imply a level of certainty about causation that is often clinically unconfirmed. Subsets of functional neurological disorders include functional neurological symptom disorder (FNsD), conversion disorder, and psychogenic movement disorder/non-epileptic seizures. Functional neurological disorders are common in neurological services, accounting for up to one third of outpatient neurology clinic attendances, and associated with as much physical disability and distress as other neurological disorders. The diagnosis is made based on positive signs and symptoms in the history and examination during consultation of a neurologist (see below). Physiotherapy is particularly helpful for patients with motor symptoms (weakness, gait disorders, movement disorders) and tailored cognitive behavioural therapy has the best evidence in patients with dissociative (non-epileptic) attacks.
  • 881
  • 21 Nov 2022
Topic Review
Circulating Cell-Free DNA Levels in Psychiatric Diseases
The cell-free DNA (cfDNA) levels are known to increase in biological fluids in various pathological conditions. However, the data on circulating cfDNA in severe psychiatric disorders, including schizophrenia, bipolar disorder (BD), and depressive disorders (DDs), is contradictory. The meta-analysis showed that the levels of total cfDNA and genomic cfDNA in patients with schizophrenia are significantly higher than in healthy donors (SMD values of 0.61 and 0.6, respectively; p < 0.00001). Data on mitochondrial cfDNA in schizophrenia were scarce. Meta-analysis in BD and DDs found no significant differences in the level of mitochondrial cfDNA. However, further research on mitochondrial and genomic cfDNA levels in psychiatric disorders is needed due to the data heterogeneity.
  • 881
  • 08 Mar 2023
Topic Review
HDAC&HAT after Cerebral Ischemia
The transcription factors and signaling proteins that play an important role in brain cell responses to ischemia undergo acetylation/deacetylation. In different cell types, the acetylation/deacetylation of different regions of non-histone proteins containing lysines occurs and HAT/HDAC activity depends on the acetylation site. Moreover, the activity of the HDACs themselves can be regulated by their acetylation/deacetylation.
  • 879
  • 19 Aug 2021
Topic Review
Antidiabetic Drugs in the Treatment of Alzheimer’s Disease
The public health burden of type 2 diabetes mellitus and Alzheimer’s disease is steadily increasing worldwide, especially in the population of older adults. Epidemiological and clinical studies suggest a possible shared pathophysiology between the two diseases and an increased risk of AD in patients with type 2 diabetes mellitus. Therefore, in recent years, there has been a substantial interest in identifying the mechanisms of action of antidiabetic drugs and their potential use in Alzheimer’s disease. Human studies in patients with mild cognitive impairment and Alzheimer’s disease have shown that administration of some antidiabetic medications, such as intranasal insulin, metformin, incretins, and thiazolidinediones, can improve cognition and memory. 
  • 876
  • 14 Apr 2023
Topic Review
Gut Microbiota Affect Neurogenesis
Adult neurogenesis (i.e., the life-long generation of new neurons from undifferentiated neuronal precursors in the adult brain) may contribute to brain repair after damage, and participates in plasticity-related processes including memory, cognition, mood and sensory functions. Among the many intrinsic (oxidative stress, inflammation, and ageing), and extrinsic (environmental pollution, lifestyle, and diet) factors deemed to impact neurogenesis, significant attention has been recently attracted by the myriad of saprophytic microorganismal communities inhabiting the intestinal ecosystem and collectively referred to as the gut microbiota. 
  • 875
  • 27 Jan 2022
Topic Review
Oxidative Stress in Autism Spectrum Disorder
Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder that comprises a complex aetiology, where a genetic component has been suggested, together with multiple environmental risk factors. Because of its increasing incidence in the paediatric population and the lack of successful curative therapies, ASD is one of the most puzzling disorders for medicine. In the last two decades and more, the relationship between oxidative stress (OS) and ASD has been recurrently documented. For this reason, the former hypothesis, according to which reactive oxygen and nitrogen species (ROS and RNS) play an important role in ASD is now a certainty. Thus, in this research, it is discussed many aspects of the role of OS in ASD. In addition, the possibility that free radicals promote lipid peroxidation, as well as an increase in other OS biomarkers are presented. Finally, the possibility of novel nutritional interventions aimed at counteracting ROS production in people with ASD is outlined. In fact, new strategies have investigated the possibility that ASD symptoms, as well behavioral anomalies may be improved after interventions using antioxidants as supplements or included in foods.
  • 875
  • 03 Feb 2023
Topic Review
Diagnosis of NREM Sleep Parasomnias
Non-rapid eye movement (NREM) sleep parasomnias mainly include confusional arousals (CA), sleep terrors (ST), and sleepwalking (SW), three clinical entities lumped together under the name of disorders of arousal (DoA).
  • 875
  • 05 May 2023
Topic Review
Spinal Cord Regeneration
Unlike peripheral nerves, axonal regeneration is limited following injury to the spinal cord. While there may be reduced regenerative potential of injured neurons, the central nervous system (CNS) white matter environment appears to be more significant in limiting regrowth. Several factors may inhibit regeneration, and their neutralization can modestly enhance regrowth. However, most investigations have not considered the cytoarchitecture of spinal cord white matter. Several lines of investigation demonstrate that axonal regeneration is enhanced by maintaining, repairing, or reconstituting the parallel geometry of the spinal cord white matter.
  • 874
  • 28 Apr 2022
Topic Review
Pathological Protein Aggregation Involved in ALS
Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disorder characterized by selective loss of lower and upper motor neurons (MNs) in the brain and spinal cord, resulting in paralysis and eventually death due to respiratory insufficiency. Pathological protein aggregates are also a feature of ALS, and occur in the form of ubiquitinated inclusions in neurons and glia.
  • 874
  • 28 Sep 2023
Topic Review
Fluoxetine for Comorbidities such as Depression and Diabetes
Among the most widespread pathologies, obesity, which is often associated with diabetes, is constantly increasing in incidence, and in parallel, neurodegenerative and mood disorders are increasingly affecting many people. For years, these pathologies have been so frequently observed in the population in a concomitant way that they are considered as comorbidities. In fact, common mechanisms are certainly at work in the etiology of these pathologies. Fluoxetine was discovered in the 1970s. Initially called LY110140, it was described as a selective 5-HT reuptake inhibitor.
  • 873
  • 07 Mar 2024
Topic Review
Pathophysiology and Therapy of Associated Features of Migraine
Migraine is a complex and debilitating disorder that is broadly recognised by its characteristic headache. The associated symptoms to migraine, apart from the painful component, are frequent, under-recognised and can be more deleterious than the headache itself. The clinical anamnesis of a headache patient should enquire about the associated symptoms, and treatment should be considered and individualised.
  • 872
  • 25 Sep 2022
Topic Review
Neurodegeneration by the Italian Proteomics Community
The growing number of patients affected by neurodegenerative disorders represents a huge problem for healthcare systems, human society, and economics. In this context, omics strategies are crucial for the identification of molecular factors involved in disease pathobiology, and for the discovery of biomarkers that allow early diagnosis, patients’ stratification, and treatment response prediction. The integration of different omics data is a required step towards the goal of personalized medicine. The Italian proteomics community is actively developing and applying proteomics approaches to the study of neurodegenerative disorders; moreover, it is leading the mitochondria-focused initiative of the Human Proteome Project, which is particularly important given the central role of mitochondrial impairment in neurodegeneration. 
  • 872
  • 04 Oct 2022
Topic Review
Pluripotent Stem Cells for Spinal Cord Injury Repair
Spinal cord injury (SCI) is a devastating condition of the central nervous system that strongly reduces the patient’s quality of life and has large financial costs for the healthcare system. Cell therapy has shown considerable therapeutic potential for SCI treatment in different animal models. Although many different cell types have been investigated with the goal of promoting repair and recovery from injury, stem cells appear to be the most promising.
  • 871
  • 10 Dec 2021
Topic Review
Group-I-mGluRs and Microglia in CNS: Focus on ALS
Microglia cells are the resident immune cells of the central nervous system. They act as the first-line immune guardians of nervous tissue and central drivers of neuroinflammation. Any homeostatic alteration that can compromise neuron and tissue integrity could activate microglia. 
  • 871
  • 03 Apr 2023
Topic Review
Ischemic Brain Injury
Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation in the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving poststroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.
  • 871
  • 28 Nov 2023
Topic Review
MicroRNA-Target Interaction Regulatory Network
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia; however, early diagnosis of the disease is challenging. Research suggests that biomarkers found in blood, such as microRNAs (miRNA), may be promising for AD diagnostics. Experimental data on miRNA–target interactions (MTI) associated with AD are scattered across databases and publications, thus making the identification of promising miRNA biomarkers for AD difficult. In response to this, a list of experimentally validated AD-associated MTIs was obtained from miRTarBase. Cytoscape was used to create a visual MTI network. STRING software was used for protein–protein interaction analysis and mirPath was used for pathway enrichment analysis. Several targets regulated by multiple miRNAs were identified, including: BACE1, APP, NCSTN, SP1, SIRT1, and PTEN. The miRNA with the highest numbers of interactions in the network were: miR-9, miR-16, miR-34a, miR-106a, miR-107, miR-125b, miR-146, and miR-181c. The analysis revealed seven subnetworks, representing disease modules which have a potential for further biomarker development. The obtained MTI network is not yet complete, and additional studies are needed for the comprehensive understanding of the AD-associated miRNA targetome. 
  • 870
  • 08 Dec 2021
Topic Review
PI3K/AKT/GSK3 Pathway Involved in Psychiatric Illnesses
Psychiatric illnesses may be qualified to the cellular impairments of the function for survival or death in neurons, which may consequently appear as abnormalities in the neuroplasticity. The molecular mechanism has not been well understood, however, it seems that PI3K, AKT, GSK3, and their downstream molecules have crucial roles in the pathogenesis. Through transducing cell surviving signal, the PI3K/AKT/GSK3 pathway may organize an intracellular central network for the action of the synaptic neuroplasticity. In addition, the pathways may also regulate cell proliferation, cell migration, and apoptosis. Several lines of evidence have supported a role for this signaling network underlying the development and treatment for psychiatric illnesses.
  • 870
  • 11 Oct 2023
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