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Topic Review
Origin and Emergence of Microglia
Microglia belong to tissue-resident macrophages of the central nervous system (CNS), representing the primary innate immune cells. This cell type constitutes ~7% of non-neuronal cells in the mammalian brain and has a variety of biological roles integral to homeostasis and pathophysiology from the late embryonic to adult brain. Its unique identity that distinguishes its “glial” features from tissue-resident macrophages resides in the fact that once entering the CNS, it is perennially exposed to a unique environment following the formation of the blood–brain barrier. Microgliogenesis is a complex biological process strictly regulated by multiple molecular drivers. The widely accepted, contemporary view of the origin of CNS-resident microglia is the yolk sac (YS). However, this was hotly debated until the early 2010s. The suggested microglial progenitors in mice are the early, c-ΜΥΒ-independent, CSF-1R+ erythro-myeloid progenitors of the YS. Additionally, it is postulated that the greatest contribution to microglial repopulation is based upon its local self-renewal, both in steady state and disease. Nevertheless, circulating monocytes may also contribute to a lesser extent, especially in disease.  
  • 609
  • 05 May 2023
Topic Review Video
Role of Mitochondria in Alzheimer’s Disease Pathogenesis
Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in the brain of extracellular plaques of amyloid-β and intracellular tangles of phosphorylated tau. The importance of mitochondrial dysfunction in AD pathogenesis, while previously underrecognized, is now more and more appreciated. Mitochondria are an essential organelle involved in cellular bioenergetics and signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, mitochondrial trafficking, mitochondrial fission, and mitochondrial fusion are dysregulated in the AD brain. Excess fission and fragmentation yield mitochondria with low energy production. Reduced glucose metabolism is also observed in the AD brain with a hypometabolic state, particularly in the temporo-parietal brain regions.
  • 609
  • 11 Feb 2024
Topic Review
Lipid Abnormalities in Cerebrotendinous Xanthomatosis
Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder caused by pathogenic variants in CYP27A1, leading to a deficiency in sterol 27-hydroxylase. This defect results in the accumulation of cholestanol and bile alcohols in various tissues, including the brain, tendons, and peripheral nerves. Elevated levels of cholestanol are consistently observed. Most patients present normal or low serum cholesterol levels. The decrease in chenodeoxycholic acid (CDCA) leads to increased synthesis of cholesterol metabolites such as bile alcohols 23S-pentol and 25-tetrol 3-glucuronide, which may serve as surrogate follow-up markers in patients with CTX. Lipid abnormalities in CTX have clinical implications. Cholestanol deposition in tissues contributes to the clinical manifestations, including neurological symptoms and tendon xanthomas. Dyslipidemia and abnormal cholesterol metabolism may also contribute to the increased risk of atherosclerosis and cardiovascular complications observed in some CTX patients.
  • 608
  • 27 Jun 2023
Topic Review
Neuropsychiatric and Neurocognitive Sequelae Following Subarachnoid Hemorrhage
Subarachnoid hemorrhage (SAH) is a medical emergency that requires immediate intervention. The etiology varies between cases; however, rupture of an intracranial aneurysm accounts for 80% of medical emergencies. Early intervention and treatment are essential to prevent long-term complications. Treatment of SAH has drastically improved, which is responsible for the rapid rise in SAH survivors. Post-SAH, a significant number of patients exhibit impairments in memory and executive function and report high rates of depression and anxiety that ultimately affect daily living, return to work, and quality of life.
  • 607
  • 25 May 2023
Topic Review
Role of Autophagy in Postischemic Brain Neurodegeneration
After cerebral ischemia, autophagy was found to be activated in neuronal, glial and vascular cells. Some studies have shown the protective properties of autophagy in postischemic brain, while other studies have shown completely opposite properties. Thus, autophagy is now presented as a double-edged sword with possible therapeutic potential in brain ischemia. 
  • 607
  • 12 Sep 2023
Topic Review
Lipids in Psychiatric Disorders
Lipids are a crucial component of the human brain, serving important structural and functional roles. They are involved in cell function, myelination of neuronal projections, neurotransmission, neural plasticity, energy metabolism, and neuroinflammation. Despite their significance, the role of lipids in the development of mental disorders has not been well understood. This review focused on the potential use of lipids as blood biomarkers for common mental illnesses, such as major depressive disorder, anxiety disorders, bipolar disorder, and schizophrenia.
  • 606
  • 08 Feb 2024
Topic Review
Cofilin Dysregulation in Stroke and Other Neurodegenerative Disorders
Cofilin is an essential protein in cytoskeletal dynamics, and any dysregulation could lead to potentially serious complications. Cofilin’s involvement is underscored by its impact on pathological hallmarks like Aβ plaques and α-synuclein aggregates, triggering synaptic dysfunction, dendritic spine loss, and impaired neuronal plasticity, leading to cognitive decline. 
  • 605
  • 23 Jan 2024
Topic Review
Connections between Intestinal Flora and Kynurenine Pathway
The intestinal flora has been the focus of numerous investigations recently, with inquiries not just into the gastrointestinal aspects but also the pathomechanism of other diseases such as nervous system disorders and mitochondrial diseases. Mitochondrial disorders are the most common type of inheritable metabolic illness caused by mutations of mitochondrial and nuclear DNA. Metabolites of the kynurenine pathway are linked to many disorders, such as depression, schizophrenia, migraine, and also diseases associated with impaired mitochondrial function. The kynurenine pathway includes many substances, for instance kynurenic acid and quinolinic acid. 
  • 605
  • 05 Mar 2024
Topic Review
COVID-19 and the Nervous System
Neuropsychiatric manifestations of viral infections (both per se and secondary to the neuroinflammatory reaction of the host) are mainly attributed to immunological reactions, so many aspects of their pathogenesis are still nuclear. Some novel therapeutic strategies are progressively emerging in which a vaccination may be having a particular impact on recovery and reduction of death. In this context, it is accepted that the SARS-CoV-2 virus is profoundly neurotropic and neuroinvasive, with various effects on the nervous system, although there is no complete understanding of the mechanism of neuroinvasion, brain injury, or short- or long-term neuropsychiatric sequelae.
  • 604
  • 12 Oct 2023
Topic Review
Biomarkers in Alzheimer’s Disease
Alzheimer’s disease (AD), as the main cause of dementia, affects millions of people around the world, whose diagnosis is based mainly on clinical criteria. Unfortunately, the diagnosis is obtained very late, when the neurodegenerative damage is significant for most patients. Therefore, the exhaustive study of biomarkers is indispensable for diagnostic, prognostic, and even follow-up support. 
  • 604
  • 11 Jan 2024
Topic Review
Radiation therapy in the Treatment of Neurological Disorders
Radiation therapy (RT) has been widely adopted in the treatment of various neurological disorders, for different aims such as pain relief, control of the symptoms, and obliteration of brain arteriovenous malformations. Moreover, RT is a non-invasive approach that can be safely adopted also in elderly patients. 
  • 603
  • 24 Oct 2022
Topic Review
Genetic Engineering of IgG Fusion Proteins
The treatment of neurological disorders with large-molecule biotherapeutics requires that the therapeutic drug be transported across the blood–brain barrier (BBB). Recombinant biotherapeutics, such as neurotrophins, enzymes, decoy receptors, and monoclonal antibodies (MAb), do not cross the BBB. These biotherapeutics can be re-engineered as brain-penetrating bifunctional IgG fusion proteins. These recombinant proteins comprise two domains, the transport domain and the therapeutic domain, respectively. The transport domain is an MAb that acts as a molecular Trojan horse by targeting a BBB-specific endogenous receptor that induces receptor-mediated transcytosis into the brain, such as the human insulin receptor (HIR) or the transferrin receptor (TfR). 
  • 602
  • 02 Aug 2022
Topic Review
Oxidative Stress in the Pathophysiology of Neurodegenerative Diseases
Oxidative stress was proposed to be involved in neurodegenerative processes and to play an important role in the morbidity and progression of various neurodegenerative disorders. Accordingly, a number of studies discovered the potential of natural plant constituents to have significant antioxidant activity.
  • 598
  • 06 Apr 2023
Topic Review
A Pathophysiological Intersection of Diabetes and Alzheimer’s Disease
Diabetes is among the most prevalent diseases of the modern world and is strongly linked to an increased risk of numerous neurodegenerative disorders, although the exact pathophysiological mechanisms are not clear yet. Insulin resistance is a serious pathological condition, connecting type 2 diabetes, metabolic syndrome, and obesity. Insulin resistance has been proven to be connected also to cognitive decline and dementias, including the most prevalent form, Alzheimer’s disease. The relationship between diabetes and Alzheimer’s disease regarding pathophysiology is so significant that it has been proposed that some presentations of the condition could be termed type 3 diabetes.
  • 595
  • 18 Oct 2022
Topic Review
Imbalance of Essential Metals in Traumatic Brain Injury
Dysfunction of the complex cerebral networks underlying wakefulness and awareness is responsible for Disorders of Consciousness (DoC). Traumatic Brain Injury (TBI) is a common cause of DoC, and it is responsible for a multi-dimensional pathological cascade that affects the proper functioning of the brainstem and brain consciousness pathways. Iron (Fe), Zinc (Zn), and Copper (Cu) have a role in the neurophysiology of both the ascending reticular activating system, a multi-neurotransmitter network located in the brainstem that is crucial for consciousness, and several brain regions.
  • 594
  • 21 Apr 2023
Topic Review
Risk Genes and Their Candidates in Multiple Sclerosis
Oligodendrocytes are central nervous system glial cells that wrap neuronal axons with their differentiated myelin membranes as biological insulators. There has recently been an emerging concept that multiple sclerosis could be triggered and promoted by various risk genes that appear likely to contribute to the degeneration of oligodendrocytes. Despite the known involvement of vitamin D, immunity, and inflammatory cytokines in disease progression, the common causes and key genetic mechanisms remain unknown.
  • 593
  • 01 Feb 2023
Topic Review
Neuropeptides and Their Roles in the Cerebellum
Although more than 30 different types of neuropeptides have been identified in various cell types and circuits of the cerebellum, their unique functions in the cerebellum remain poorly understood. Given the nature of their diffuse distribution, peptidergic systems are generally assumed to exert a modulatory effect on the cerebellum via adaptively tuning neuronal excitability, synaptic transmission, and synaptic plasticity within cerebellar circuits. Moreover, cerebellar neuropeptides have also been revealed to be involved in the neurogenetic and developmental regulation of the developing cerebellum, including survival, migration, differentiation, and maturation of the Purkinje cells and granule cells in the cerebellar cortex. On the other hand, cerebellar neuropeptides hold a critical position in the pathophysiology and pathogenesis of many cerebellar-related motor and psychiatric disorders, such as cerebellar ataxias and autism. A growing body of evidence has indicated neuropeptides as potential therapeutic targets to ameliorate these diseases effectively. 
  • 593
  • 21 Feb 2024
Topic Review
Gene-Environment Interactions in Schizophrenia
Schizophrenia is a devastating mental illness with a strong genetic component that is the subject of extensive research. Despite the high heritability, it is well recognized that non-genetic factors such as certain infections, cannabis use, psychosocial stress, childhood adversity, urban environment, and immigrant status also play a role. Whenever genetic and non-genetic factors co-exist, interaction between the two is likely. This means that certain exposures would only be of consequence given a specific genetic makeup.
  • 592
  • 06 Dec 2021
Topic Review
Cannabinoid Locations in the Central Nervous System
Neuroinflammation is a complex biological process that typically originates as a protective response in the brain. This inflammatory process is triggered by the release of pro-inflammatory substances like cytokines, prostaglandins, and reactive oxygen and nitrogen species from stimulated endothelial and glial cells, including those with pro-inflammatory functions, in the outer regions. While neuronal inflammation is common in various central nervous system disorders, the specific inflammatory pathways linked with different immune-mediated cell types and the various factors influencing the blood-brain barrier significantly contribute to disease-specific characteristics.
  • 592
  • 11 Oct 2023
Topic Review
Telehealth in Neurodegenerative Diseases
Telehealth is the distribution of health-related services using electronic technologies, improving the continuity of care in patients with chronic neurodegenerative disorders. 
  • 591
  • 31 Mar 2021
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