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Topic Review
Yeast as a Model for VPS13-Dependent Neurodegenerative Diseases
Mutations in human VPS13A-D genes result in rare neurological diseases, including chorea-acanthocytosis (ChAc). The pathogenesis of these diseases is poorly understood, and no effective treatment is available. As VPS13 genes are evolutionarily conserved, the effects of the pathogenic mutations could be studied in model organisms, including yeast, where one VPS13 gene is present. Here, the researchers summarize advancements obtained using yeast. In recent studies, vps13Δ and vps13-I2749 yeast mutants, which are models of chorea-acanthocytosis, were used to screen for multicopy and chemical suppressors. Two of the suppressors, a fragment of the MYO3 and RCN2 genes, act by downregulating calcineurin activity. In addition, vps13Δ suppression was achieved by using calcineurin inhibitors. The other group of multicopy suppressors were genes: FET4, encoding iron transporter, and CTR1, CTR3 and CCC2, encoding copper transporters. Mechanisms of their suppression rely on causing an increase in the intracellular iron content. Moreover, among the identified chemical suppressors were copper ionophores, which require a functional iron uptake system for activity, and flavonoids, which bind iron. These findings point at areas for further investigation in a higher eukaryotic model of VPS13-related diseases and to new therapeutic targets: calcium signalling and copper and iron homeostasis. Furthermore, the identified drugs are interesting candidates for drug repurposing for these diseases.
  • 971
  • 18 May 2022
Topic Review
Lysophospholipids for Neurodegenerative Disorders
Neurodegenerative diseases (NDs) commonly present misfolded and aggregated proteins. Considerable research has been performed to unearth the molecular processes underpinning this pathological aggregation and develop therapeutic strategies targeting NDs. Fibrillary deposits of α-synuclein (α-Syn), a highly conserved and thermostable protein, are a critical feature in the development of NDs such as Alzheimer’s disease (AD), Lewy body disease (LBD), Parkinson’s disease (PD), and multiple system atrophy (MSA). Inhibition of α-Syn aggregation can thus serve as a potential approach for therapeutic intervention. The degradation of target proteins by small molecules has emerged as a new therapeutic modality, gaining the hotspot in pharmaceutical research. Additionally, interest is growing in the use of food-derived bioactive compounds as intervention agents against NDs via functional foods and dietary supplements. According to reports, dietary bioactive phospholipids may have cognition-enhancing and neuroprotective effects, owing to their abilities to influence cognition and mental health in vivo and in vitro. 
  • 971
  • 20 Dec 2022
Topic Review
The Neuromodulatory Role of the Noradrenergic System
The noradrenergic system is one of four primary neuromodulatory systems. It plays an important function in altering basic synaptic transmission patterns. The groups of neurons responsible for the delivery of the neuromodulators are known as ascending neuromodulatory systems. Norepinephrine (NE) has classically been viewed as a major mediator of arousal that plays an important role in regulating cognition, perception, and sensory processing.
  • 970
  • 01 Aug 2022
Topic Review
Arcuate Neurocircuits
Obesity is a chronic state of energy imbalance that represents a major public health problem and greatly increases the risk for developing hypertension, hyperglycemia, and a multitude of related pathologies that encompass the metabolic syndrome. The underlying mechanisms and optimal treatment strategies for obesity, however, are still not fully understood. A growing area of research is to better understand how peripheral hormones interact with a widely distributed network of brain circuits involved in the control of energy balance. In this regard, the arcuate nucleus of the hypothalamus has emerged as an important brain region due to its ability to sense circulating hormones and to modulate neural pathways controlling food intake and energy expenditure, and blood pressure.
  • 967
  • 22 Jul 2021
Topic Review
Mass Spectrometry for Neurobiomarker Discovery: Post-Translational Modifications Relevance
Neurodegenerative diseases are incurable, heterogeneous, and age-dependent disorders that challenge modern medicine. A deeper understanding of the pathogenesis underlying neurodegenerative diseases is necessary to solve the unmet need for new diagnostic biomarkers and disease-modifying therapy and reduce these diseases’ burden. Specifically, post-translational modifications (PTMs) play a significant role in neurodegeneration. Due to its proximity to the brain parenchyma, cerebrospinal fluid (CSF) has long been used as an indirect way to measure changes in the brain. Mass spectrometry (MS) analysis in neurodegenerative diseases focusing on PTMs and in the context of biomarker discovery has improved and opened venues for analyzing more complex matrices such as brain tissue and blood. Notably, phosphorylated tau protein, truncated α-synuclein, APP and TDP-43, and many other modifications were extensively characterized by MS. Great potential is underlying specific pathological PTM-signatures for clinical application. This review focuses on PTM-modified proteins involved in neurodegenerative diseases and highlights the most important and recent breakthroughs in MS-based biomarker discovery.
  • 967
  • 13 Apr 2022
Topic Review
Duchenne’s Muscular Dystrophy
Duchenne Muscular Dystrophy (DMD) is an X-linked, degenerative, neuro-muscular disorder with an estimated male birth incidence of 1:3800 to 1:6200. The disease is characterized by a progressive degeneration of muscle fibres resulting in muscle weakness and eventual loss of ambulation. Functional dependence typically occurs in the second decade of life with cardiac and respiratory complications often shortening life. Other types of muscular dystrophies, such as Becker’s muscular dystrophy (BMD) and limb-girdle muscular dystrophy (LGMD), have similar progression to DMD but a near normal life expectancy with symptoms appearing later, being less severe, and thus preserving ambulation often to mid-life.
  • 963
  • 23 Mar 2021
Topic Review
Correlation between Phenotype and Genotype in CTNNB1 Syndrome
The CTNNB1 (Cadherin-associated protein, beta 1) Syndrome is a rare neurodevelopmental disorder associated with developmental delay, intellectual disability, and delayed or absent speech. Research showed wide genotypic and phenotypic variability in patients with CTNNB1 Syndrome. The most common moderate-severe phenotype manifested in facial dysmorphisms, microcephaly, various motor disabilities, language and cognitive impairments, and behavioral abnormalities (e.g., autistic-like or aggressive behavior).
  • 963
  • 05 Dec 2022
Topic Review
Deep Brain Stimulation for Refractory Neurological Disorder Management
Deep brain stimulation (DBS) has been extensively studied due to its reversibility and significantly fewer side effects. DBS is mainly a symptomatic therapy, but the stimulation of subcortical areas by DBS is believed to affect the cytoarchitecture of the brain, leading to adaptability and neurogenesis. The neurological disorders most commonly studied with DBS were Parkinson’s disease, essential tremor, obsessive-compulsive disorder, and major depressive disorder. 
  • 963
  • 22 Dec 2023
Topic Review
Effect of Physical Exercise in Alzheimer’s Disease Patients
Physical exercise (PE) can be a non-pharmacological intervention in delaying cognitive decline in patients with Alzheimer’s disease (AD) not only by improving cardiovascular fitness but also by attenuating neuroinflammation. Animal studies consistently report that PE improves cardiovascular fitness and attenuates AD-promoting processing of amyloid precursor protein and neuroinflammation, facilitates brain clearance of toxic amyloid β peptides and oligomers and promotes brain connectivity and nerve cell viability. Further studies in human are necessary to develop optimal, personalised protocols to take full advantage of the beneficial effects of PE that promote cardiovascular fitness, attenuate systemic inflammation, stimulate brain amyloid β peptides brain catabolism, delay immunescence and support brain clearance of amyloid β peptides and their catabolism in peripheral organs.
  • 963
  • 06 May 2022
Topic Review
Core Techniques for Tailoring of The Cranio-Orbito-Zygomatic Approach
The cranio-orbito-zygomatic (COZ) approach is an extension of the pterional approach, involving the adjunct of orbitozygomatic (OZ) osteotomy to allow wider exposure of the anterior and middle skull base and upper retroclival region. It provides advantages in giant aneurysms of the anterior communicating artery (ACoA) and distal basilar artery, tuberculum sellae, large anterior clinoidal, spheno-orbital meningiomas, large craniopharyngiomas, giant pituitary adenomas, cavernous hemangiomas of the hypothalamus, and crus cerebri of the midbrain.
  • 962
  • 07 Apr 2022
Topic Review
Carnosic Acid and Mechanisms of Neuroprotection
Carnosic acid (CA) is a diterpenoid abundantly present in plants belonging to the genus Rosmarinus and Salvia of the family Lamiaceae, accounting for their application in traditional medicine. CA exerts its neuroprotective effects through a diverse range of mechanisms, some of which include the prevention of amyloid-β (Aβ)-induced neurodegeneration, induction of autophagy, alleviation of oxidative stress and via anti-apoptotic effects.
  • 961
  • 27 Mar 2023
Topic Review
Resting State fMRI in ASD
Autism spectrum disorder (ASD) is characterized by a fundamental change in self-awareness including seemingly paradoxical features like increased ego-centeredness and weakened self-referentiality.
  • 961
  • 10 Dec 2021
Topic Review
Plant Extract of Limonium gmelinii
L. gmelinii is widespread in Eastern Europe, South-Western Siberia, China, and Central Asia. It has industrial resources on the whole territory of Kazakhstan, primarily on saline lands, and has been used in traditional herbal medicine in Central Asia for hundreds of years. These plants are characterized by rapid growth and high yield, so their reserves in nature can be kept at their original level if the guidelines of good practices for collection and preparation of medicinal plant raw materials are followed. These plants can also be cultivated.
  • 960
  • 28 Mar 2022
Topic Review
Environmental Enrichment Effects in the Cerebellum
The cerebellum is a very plastic brain region that responds to every experience with deep structural and functional rearrangement.
  • 960
  • 18 May 2022
Topic Review
Obesity-Induced Neuroinflammation
Obesity-induced neuroinflammation is a chronic aseptic central nervous system inflammation that presents systemic characteristics associated with increased pro-inflammatory cytokines such as interleukin 1 beta (IL-1β) and interleukin 18 (IL-18) and the presence of microglia and reactive astrogliosis as well as the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. The obesity pandemic is associated with lifestyle changes, including an excessive intake of obesogenic foods and decreased physical activity. Brain areas such as the lateral hypothalamus (LH), lateral septum (LS), ventral tegmental area (VTA), and nucleus accumbens (NAcc) have been implicated in the homeostatic and hedonic control of feeding in experimental models of diet-induced obesity. A chronic lipid intake triggers neuroinflammation in several brain regions such as the hypothalamus, hippocampus, and amygdala.
  • 960
  • 19 Jan 2023
Topic Review
Phyto-Nanotechnology for the Treatment of Neurodegenerative Disorders
The strategies involved in the development of therapeutics for neurodegenerative disorders are very complex and challenging due to the existence of the blood-brain barrier (BBB), a closely spaced network of blood vessels and endothelial cells that functions to prevent the entry of unwanted substances in the brain. The emergence and advancement of nanotechnology shows favourable prospects to overcome this phenomenon. Engineered nanoparticles conjugated with drug moieties and imaging agents that have dimensions between 1 and 100 nm could potentially be used to ensure enhanced efficacy, cellular uptake, specific transport, and delivery of specific molecules to the brain, owing to their modified physico-chemical features. The conjugates of nanoparticles and medicinal plants, or their components known as nano phytomedicine, have been gaining significance lately in the development of novel neuro-therapeutics owing to their natural abundance, promising targeted delivery to the brain, and lesser potential to show adverse effects.
  • 959
  • 08 Feb 2022
Topic Review
Amyotrophic Lateral Sclerosis with the Enteric Nervous System
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present a clinical phenotype of classic ALS—with predominant atrophy, muscle weakness, and fasciculations—and survival of 3 to 5 years following diagnosis. There are two types of ALS: the familial form with genetic involvement, and the sporadic form with a multifactorial origin. ALS pathophysiology is characterized by involvement of multiple processes, including oxidative stress, glutamate excitotoxicity, and neuroinflammation. Moreover, it is proposed that conditioning risk factors affect ALS development—such as susceptibility to neurodegeneration in motor neurons, the intensity of performed physical activity, and intestinal dysbiosis with involvement of the enteric nervous system—which supports the existing theories of disease generation.
  • 959
  • 14 Apr 2023
Topic Review
Drug Development against Parkinson’s Disease
Parkinson’s disease (PD) is currently the second most common neurodegenerative disease among the older population. The main problem in the treatment is that the exact etiology of the disease is not known, and it is not known what exactly initiates the neuronal damage process. There is still no drug that would effectively cure the disease. However, scientists are still trying to develop more effective pharmacotherapy by using new molecular targets based on relevant in vitro and in vivo models, and by using computer-aided design of drugs and other particles.
  • 956
  • 01 Jul 2021
Topic Review
Catatonia: Diagnosis, Treatment and Clinical Challenges
Catatonia is a syndrome that has been associated with several mental illness disorders but that has also presented as a result of other medical conditions. It is defined as a group of symptoms that involve a lack of movement as well as a lack of communication. It can be accompanied by agitation, confusion, and restlessness. Schizophrenia and other psychiatric disorders such as mania and depression are known to be associated with catatonia. The treatment of catatonia often involves the use of benzodiazepines, such as lorazepam, that can be used in combination therapy with antipsychotics. Definitive treatment may be found with electroconvulsive therapy (ECT).
  • 956
  • 07 Dec 2021
Topic Review
Monitoring Macromolecules Directly from the Cerebral Interstitial Fluid
There are only a few techniques available that allow for the direct sampling from the cerebral interstitial space and thus provide insight into real concentrations in the brain parenchyma. Such techniques are microdialysis, cerebral open flow microperfusion (cOFM), and biosensors. Innovations in the field are discussed, along with the ‘nuts and bolts’ of the techniques.
  • 956
  • 22 Jun 2022
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