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Topic Review
Pharmacological Activities of Diterpenoid Alkaloids
Diterpenoid alkaloids (DAs) are characteristic components of some genera of the Ranunculaceae family, the occurrence of which is extraordinarily high in the genera Aconitum, Delphinium, and Consolida. To affect the central nervous system, primarily, the drug should pass the blood–brain barrier (BBB). Transmembrane diffusion is the most common route of drugs to pass the BBB and, in contrast to the transport system, shows a non-saturable kinetic. Physiochemical features of the drug mainly determine the amounts of this passage. Molecular weight (400–600 Da is optimum), lipid solubility, molecular charge, and tertiary structure are the most important factors necessary for transmembrane diffusion through BBB. The diterpenic backbone of DAs provides their suitable lipid solubility, but the presence of tertiary nitrogen makes them different from normal diterpenoids. The tertiary nitrogen with the highest proton affinity in the molecule (in water) rearranges the electronic structure of DA by its protonation. Moreover, computational modeling showed that the function of nitrogen besides ester sidechains causes DAs to interact with the active sites as well as their toxicity.
  • 718
  • 22 May 2023
Topic Review
Traumatic Cerebral Haemorrhage
Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. For all ages and TBI severities, crude incidence rates ranged from 47.3 to 694 per 100,000 population per year (country-level studies) and from 83.3 to 849 per 100,000 population per year (regional-level studies).
  • 717
  • 07 Feb 2022
Topic Review
Neuroanatomical Correlates of Anxiety Disorders
Developing an anxiety disorder can be the source of further cognitive, behavioral, and emotional struggles, impacting the quality of life of people experiencing such disorders and leading to a burden on health systems. Increased knowledge of the neurobiological events leading to the development of such disorders can be crucial for diagnostic procedures, as well as the selection and adaptation of therapeutic and preventive measures. Despite recent advances in this field, research is still at the initial steps when it comes to understanding the specific neurofunctional processes guiding these changes in the brains of people with an anxiety disorder. 
  • 717
  • 15 Apr 2024
Topic Review
Neuronal Cytoskeleton in Intellectual Disability
Intellectual disability (ID) is a condition characterized by limited intellectual functioning and adaptive behaviors. It affects 1–3% of the worldwide population and no pharmacological therapies are currently available. Too many genes have been found mutated in ID patients suggesting that the genetic bases are highly heterogeneous and apparently unrelated. Bibliomic analysis reveals that ID genes converge onto a few biological modules, one of these being cytoskeleton dynamics and Rho GTPases transduction. Genetic variants exert their effects at different levels in a hierarchical arrangement, starting from the molecular level and moving toward higher levels of organization, i.e., cell compartment and functions, circuits, cognition, and behavior. Thus, cytoskeleton alterations which have an impact on cell processes such as neuronal migration, neuritogenesis, and synaptic plasticity, rebound on the overall establishment of an effective network and consequently on the cognitive phenotype. Systems biology approaches are more focused on the overall interconnected network rather than on individual genes, encouraging the design of therapies that aim to correct common dysregulated biological processes. This review summarizes current knowledge about cytoskeleton control in neurons and its relevance for the ID pathogenesis, exploiting in silico modeling and translating the implications of those findings to biomedical research.
  • 716
  • 18 Jun 2021
Topic Review
Association Between Glycaemic Imbalances with Seizures and Epilepsy
Cerebral excitability and systemic metabolic balance are closely interconnected. Energy supply to neurons depends critically on glucose, whose fluctuations can promote immediate hyperexcitability resulting in acute symptomatic seizures. On the other hand, chronic disorders of sugar metabolism (e.g., diabetes mellitus) are often associated with long-term epilepsy. 
  • 716
  • 18 Apr 2023
Topic Review
Decoding Neurodegeneration
Neurodegenerative disorders often acquire due to genetic predispositions and genomic alterations after exposure to multiple risk factors. The most commonly found pathologies are variations of dementia, such as frontotemporal dementia and Lewy body dementia, as well as rare subtypes of cerebral and cerebellar atrophy-based syndromes. In an emerging era of biomedical advances, molecular–cellular studies offer an essential avenue for a thorough recognition of the underlying mechanisms and their possible implications in the patient’s symptomatology. 
  • 716
  • 04 Sep 2023
Topic Review
Psychiatric Partial Hospitalization Programs
The World Health Organization (WHO) developed a 7-year Mental Health Action Plan in 2013, which recommends integration of health and social care services into community-based settings, implementation of strategies for health promotion and prevention of illness, and support of research. In this entry, we highlight partial hospitalization programs (PHPs) for delusional disorder (DD), with a special focus on the health and psychosocial needs of women.
  • 714
  • 19 May 2021
Topic Review
CK1δ-peptides modulating metabolism of APP
Alzheimer’s disease (AD) is the major cause of dementia, and affected individuals suffer from severe cognitive, mental, and functional impairment. Histologically, AD brains are basically characterized by the presence of amyloid plaques and neurofibrillary tangles. Previous reports demonstrated that protein kinase CK1δ influences the metabolism of amyloid precursor protein (APP) by inducing the generation of amyloid-β (Aβ), finally contributing to the formation of amyloid plaques and neuronal cell death. CK1δ as a promising therapeutic target and suggested an innovative strategy for the treatment of AD based on peptide therapeutics specifically modulating the interaction between CK1δ and APP. Initially, CK1δ-derived peptides manipulating the interactions between CK1δ and APP695 were identified by interaction and phosphorylation analysis in vitro. Selected peptides subsequently proved their potential to penetrate cells without inducing cytotoxic effects. Finally, for at least two of the tested CK1δ-derived peptides, a reduction in Aβ levels and amyloid plaque formation could be successfully demonstrated in a complex cell culture model for AD. Consequently, the presented results provide new insights into the interactions of CK1δ and APP695 while also serving as a promising starting point for further development of novel and highly innovative pharmacological tools for the treatment of AD. 
  • 714
  • 25 Jun 2021
Topic Review
Targeting Microglia-Synapse Interactions
Synaptic plasticity refers to the capability of experience to modify neural circuit function and thereby influence thinking, feeling, and behavioral patterns.
  • 712
  • 28 Apr 2021
Topic Review
Lithium and hPOA Neurons
Lithium (Li+) salt is widely used as a therapeutic agent for treating neurological and psychiatric disorders. Despite its therapeutic effects on neurological and psychiatric disorders, it can also disturb the neuroendocrine axis in patients under lithium therapy. The hypothalamic area is involved in the physiological control of anterior pituitary hormones and the regulation of the neuroendocrine system. Li+ can modulate neuronal properties and a neurotransmitter system in various neuronal populations. However, the effect of Li+ on hypothalamic neuronal excitability has not been fully understood yet.
  • 710
  • 19 Apr 2021
Topic Review
Quinones as Neuroprotective Agents
Quinones can in principle be viewed as a double-edged sword in the treatment of neurodegenerative diseases, since they are often cytoprotective but can also be cytotoxic due to covalent and redox modification of biomolecules. Nevertheless, low doses of moderately electrophilic quinones are generally cytoprotective, mainly due to their ability to activate the Keap1/Nrf2 pathway and thus induce the expression of detoxifying enzymes. Some natural quinones have relevant roles in important physiological processes. One of them is coenzyme Q10, which takes part in the oxidative phosphorylation processes involved in cell energy production, as a proton and electron carrier in the mitochondrial respiratory chain, and shows neuroprotective effects relevant to Alzheimer’s and Parkinson’s diseases. Additional neuroprotective quinones that can be regarded as coenzyme Q10 analogues are idobenone, mitoquinone and plastoquinone.
  • 710
  • 08 Aug 2023
Topic Review
The NLRP3 Inflammasome in Cerebrovascular Diseases
The nucleotide-binding and oligomerization (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3) inflammasome is one of the most comprehensively investigated inflammasomes. An inflammasome is a multiple protein complex, which comprised of sensor proteins such as pattern recognition receptors (PRRs), an effector protein (i.e., caspase-1 in canonical inflammasome, and caspase-4,5,11 in non-canonical inflammasome), and an adaptor protein (i.e., apoptosis-associated speck-like protein, ASC—containing caspase activation and recruitment domain, CARD). In the presence of cardio-cerebrovascular disease risk factors such as aging, hypertension, type-2 diabetes mellitus (T2DM), and cerebral amyloid angiopathy (CAA) mediated by vascular deposition of β-amyloid, the common underlying pathophysiological mechanisms of CSVD are primarily linked to thrombo-inflammation and arteriolosclerosis of penetrating cerebral micro-vessels (50–400 μm in diameter).
  • 709
  • 03 Feb 2023
Topic Review
Cognitive Impairment Following the History of Multiple Sclerosis
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and degenerative disease of the central nervous system (CNS). Tracing the history of MS, from the first descriptions of the disease to the present day, is not only important from a historical or social viewpoint: the reconstruction of this path allows to understand, for example, how the cognitive impairments and psycho-emotional disorders which characterize MS are under-recognized or variously interpreted, even today.
  • 709
  • 28 Feb 2023
Topic Review
Role of NMNAT2/SARM1 in Neuropathy Development
Chemotherapy-induced peripheral neuropathy (CIPN) commonly arises as a side effect of diverse cancer chemotherapy treatments. This condition presents symptoms such as numbness, tingling, and altered sensation in patients, often accompanied by neuropathic pain. Pathologically, CIPN is characterized by an intensive “dying-back” axonopathy, starting at the intra-epidermal sensory innervations and advancing retrogradely. The lack of comprehensive understanding regarding its underlying mechanisms explains the absence of effective treatments for CIPN. Recent investigations into axon degeneration mechanisms have pinpointed nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) and sterile alpha and TIR motif-containing 1 protein (SARM1) as pivotal mediators of injury-induced axonal degeneration. 
  • 709
  • 23 Feb 2024
Topic Review
Conventional MRI Characteristics of Peri- and Para-Vascular Spaces
Brain spaces around (perivascular spaces) and alongside (paravascular or Virchow–Robin spaces) vessels have gained significant attention due to the advancements of in vivo imaging tools and to their crucial role in maintaining brain health, contributing to the anatomic foundation of the glymphatic system. In fact, it is widely accepted that peri- and para-vascular spaces function as waste clearance pathways for the brain for materials such as ß-amyloid by allowing exchange between cerebrospinal fluid and interstitial fluid. Visible brain spaces on magnetic resonance imaging are often a normal finding, but they have also been associated with a wide range of neurological and systemic conditions, suggesting their potential as early indicators of intracranial pressure and neurofluid imbalance.
  • 707
  • 01 Feb 2024
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.  
  • 705
  • 05 May 2023
Topic Review
Applications of Artificial Intelligence in Stroke and Epilepsy
Neurology is a quickly evolving specialty that requires clinicians to make precise and prompt diagnoses and clinical decisions based on the latest evidence-based medicine practices. In all Neurology subspecialties—Stroke and Epilepsy in particular—clinical decisions affecting patient outcomes depend on neurologists accurately assessing patient disability. Artificial intelligence [AI] can predict the expected neurological impairment from an AIS [Acute Ischemic Stroke], the possibility of ICH [IntraCranial Hemorrhage] expansion, and the clinical outcomes of comatose patients.
  • 705
  • 11 Mar 2024
Topic Review
Diet and Mechanisms of Multiple Sclerosis Pathology
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation and neurodegeneration. The most prominent clinical features include visual loss and sensorimotor symptoms and mainly affects those of young age. Some of the factors affecting its pathogenesis are genetic and/or environmental including viruses, smoking, obesity, and nutrition. 
  • 704
  • 01 Apr 2022
Topic Review
Role of the Histaminergic System in Migraines
The histaminergic system may play an important role in migraine pathophysiology, and dietary histamine, similar to other chemical dietary triggers, may play a role in some individuals suffering from migraines.
  • 703
  • 23 May 2023
Topic Review
Biomarkers of Dementia with Lewy Bodies
Dementia with Lewy Bodies (DLB) presents certain clinical specificities such as visual illusions or hallucinations and fluctuations in attention, but also a particular sensitivity to neuroleptics. Despite the very high diagnostic specificity of these criteria (the specificity of probable DLB is 95.1% in early stages and 88% in late stages), their sensitivity remains low (32%) in pure DLB or even lower (12%) when associated with Alzheimer’s disease (AD). In other words, DLB is still a largely underdiagnosed disease in more than two-thirds of cases. It is therefore essential to discover new biomarkers that can distinguish DLB from AD to improve differential diagnosis.
  • 702
  • 01 Jul 2022
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