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1.
Withania somnifera in Neurological Disorders: Ethnopharmacological Evidence, Mechanism of Action and its Progress in Delivery Systems.
Syed, AA, Reza, MI, Singh, P, Thombre, GK, Gayen, JR
Current drug metabolism. 2021;(7):561-571
Abstract
BACKGROUND The underlying cause of major neurodegenerative disorders remains a healthcare mystery. The thoroughly investigated causes include oxidative stress, inflammation, environmental factor, mitochondrial dysfunction, and irregular neuronal protein aggregation. Withania somnifera has been used for more than 2500 years as a useful medicinal plant to improve disease defense, prevent aging, rejuvenate the body in a vulnerable situation, and generate a feeling of mental well-being. However, a persuasive paper emphasizing its neuroprotective nature is missing. OBJECTIVE In the current review, we have delineated the protective role of W. somnifera against various neurological disorders and its progress in delivery systems. METHODS The database used in the retrieval of data were PubMed, Scopus, Science direct, and SciFinder. The keywords used were W. somnifera, Ashwagandha, neuroprotective activities, etc. The principal source of the data retrieval includes research articles, review papers, and short communications from reputed publishers, including the New England Journal of Medicine, Elsevier, Nature, Springer, and Taylor & Francis. RESULTS After an extensive literature review, we found that W. somnifera mitigates various neurological disorders, including Parkinson's disease, Alzheimer's disease, Huntington disease, tardive dyskinesia, stroke, and anxiety. Furthermore, natural compounds in nano sizes range possess better neuroprotective activity. Consequently, polymeric nanomicelles, nanoparticles, and nanofibers of natural products are used in the treatment of neurodegenerative diseases. CONCLUSION The current review substantially deciphered the protective role of W. somnifera against various neurological disorders. However, future studies are further required better to understand the molecular mechanisms behind their neuroprotective nature.
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2.
A SARS-CoV-2 -human metalloproteome interaction map.
Chasapis, CT, Georgiopoulou, AK, Perlepes, SP, Bjørklund, G, Peana, M
Journal of inorganic biochemistry. 2021;:111423
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Abstract
The recent pandemic caused by the novel coronavirus resulted in the greatest global health crisis since the Spanish flu pandemic of 1918. There is limited knowledge of whether SARS-CoV-2 is physically associated with human metalloproteins. Recently, high-confidence, experimentally supported protein-protein interactions between SARS-CoV-2 and human proteins were reported. In this work, 58 metalloproteins among these human targets have been identified by a structure-based approach. This study reveals that most human metalloproteins interact with the recently discovered SARS-CoV-2 orf8 protein, whose antibodies are one of the principal markers of SARS-CoV-2 infections. Furthermore, this work provides sufficient evidence to conclude that Zn2+ plays an important role in the interplay between the novel coronavirus and humans. First, the content of Zn-binding proteins in the involved human metalloproteome is significantly higher than that of the other metal ions. Second, a molecular linkage between the identified human Zn-binding proteome with underlying medical conditions, that might increase the risk of severe illness from the SARS-CoV-2 virus, has been found. Likely perturbations of host cellular metal homeostasis by SARS-CoV-2 infection are highlighted.
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3.
Role of ferroptosis in neurological diseases.
Yao, MY, Liu, T, Zhang, L, Wang, MJ, Yang, Y, Gao, J
Neuroscience letters. 2021;:135614
Abstract
Ferroptosis is a newly identified form of nonapoptotic regulated cell death (RCD) characterized by iron-dependent accumulation of lipid peroxides which leads to oxidative stress and cell death. Recent studies have indicated that ferroptosis plays an essential role in the pathology of neurological diseases, such as intracerebral hemorrhage, ischemic stroke, epilepsy, neurodegenerative diseases, traumatic brain injury and brain cancer. This review focuses on the latest researches on the relationship of ferroptosis with nervous system diseases, highlighting the ferroptosis-based mechanisms, and elaborating the new perspective therapeutic targets of neurological disorders.
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Active site variants in STT3A cause a dominant type I congenital disorder of glycosylation with neuromusculoskeletal findings.
Wilson, MP, Garanto, A, Pinto E Vairo, F, Ng, BG, Ranatunga, WK, Ventouratou, M, Baerenfaenger, M, Huijben, K, Thiel, C, Ashikov, A, et al
American journal of human genetics. 2021;(11):2130-2144
Abstract
Congenital disorders of glycosylation (CDGs) form a group of rare diseases characterized by hypoglycosylation. We here report the identification of 16 individuals from nine families who have either inherited or de novo heterozygous missense variants in STT3A, leading to an autosomal-dominant CDG. STT3A encodes the catalytic subunit of the STT3A-containing oligosaccharyltransferase (OST) complex, essential for protein N-glycosylation. Affected individuals presented with variable skeletal anomalies, short stature, macrocephaly, and dysmorphic features; half had intellectual disability. Additional features included increased muscle tone and muscle cramps. Modeling of the variants in the 3D structure of the OST complex indicated that all variants are located in the catalytic site of STT3A, suggesting a direct mechanistic link to the transfer of oligosaccharides onto nascent glycoproteins. Indeed, expression of STT3A at mRNA and steady-state protein level in fibroblasts was normal, while glycosylation was abnormal. In S. cerevisiae, expression of STT3 containing variants homologous to those in affected individuals induced defective glycosylation of carboxypeptidase Y in a wild-type yeast strain and expression of the same mutants in the STT3 hypomorphic stt3-7 yeast strain worsened the already observed glycosylation defect. These data support a dominant pathomechanism underlying the glycosylation defect. Recessive mutations in STT3A have previously been described to lead to a CDG. We present here a dominant form of STT3A-CDG that, because of the presence of abnormal transferrin glycoforms, is unusual among dominant type I CDGs.
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Clinical Role of Smartphone Fundus Imaging in Diabetic Retinopathy and Other Neuro-retinal Diseases.
Pujari, A, Saluja, G, Agarwal, D, Sinha, A, P R, A, Kumar, A, Sharma, N
Current eye research. 2021;(11):1605-1613
Abstract
Purpose: In today's life, many electronic gadgets have the potential to become invaluable health care devices in future. The gadgets in this category include smartphones, smartwatches, and others. Till now, smartphone role has been highlighted on many occasions in different areas, and they continue to possess immense role in clinical documentation, clinical consultation, and digitalization of ocular care. In last one decade, many treatable conditions including diabetic retinopathy, glaucoma, and other pediatric retinal diseases are being imaged using smartphones.Methods: To comprehend this cumulative knowledge, a detailed medical literature search was conducted on PubMed/Medline, Scopus, and Web of Science till February 2021.Results: The included literature revealed a definitive progress in posterior segment imaging. From simple torch light with smartphone examination to present day compact handy devices with artificial intelligence integrated software's have changed the very perspectives of ocular imaging in ophthalmology. The consistently reproducible results, constantly improving imaging techniques, and most importantly their affordable costs have renegotiated their role as effective screening devices in ophthalmology. Moreover, the obtained field of view, ocular safety, and their key utility in non-ophthalmic specialties are also growing.Conclusions: To conclude, smartphone imaging can now be considered as a quick, cost-effective, and digitalized tool for posterior segment screenings, however, their definite role in routine ophthalmic clinics is yet to be established.
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Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity.
Carroccio, A, Soresi, M, Chiavetta, M, La Blasca, F, Compagnoni, S, Giuliano, A, Fayer, F, Mandreucci, F, Castellucci, D, Seidita, A, et al
Nutrients. 2021;(6)
Abstract
BACKGROUND Non-Celiac Wheat Sensitivity (NCWS) is characterized by both intestinal and extra-intestinal symptoms. The study aims to investigate the frequency of neuropsychiatric manifestations in NCWS patients and identify their clinical and demographic characteristics. METHODS 278 clinical records of NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge between 2006 and 2020, were retrospectively revised. Fifty-two patients with Celiac Disease (CD) and 54 patients with Irritable Bowel Syndrome (IBS) served as controls. RESULTS 87% of the NCWS patients had an IBS-like clinical presentation. The NCWS group showed a longer duration of symptoms, a higher frequency of positive serum anti-nuclear antibodies than CD and IBS patients, and a higher frequency of DQ2/DQ8 haplotypes and duodenal mucosa lymphocytosis than IBS controls. In addition, 50% of NCWS patients showed neuropsychiatric manifestations, while lower percentages were observed in CD (25%) and IBS (28%) controls. Neuropsychiatric symptoms in NCWS were more frequently associated with the male sex, longer duration of symptoms, and IBS-diarrhea-like clinical presentation. CONCLUSIONS Our data suggest that in patients with IBS-like symptoms and neuropsychiatric manifestations of unknown cause, it could be useful to investigate a correlation of these symptoms with wheat ingestion to identify NCWS patients with this 'atypical' manifestation.
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Role of Hydrogen Sulfide and Polysulfides in Neurological Diseases: Focus on Protein S-Persulfidation.
Sun, HJ, Wu, ZY, Nie, XW, Bian, JS
Current neuropharmacology. 2021;(6):868-884
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Abstract
Hydrogen sulfide (H2S) and hydrogen polysulfides are recognized as important signaling molecules that are generated physiologically in the body, including the central nervous system (CNS). Studies have shown that these two molecules are involved in cytoprotection against oxidative stress and inflammatory response. In the brain system, H2S and polysulfides exert multiple functions in both health and diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), memory decline, and glioma. Mechanistically, S-Persulfidation (also known as S-sulfuration or S-sulfhydration) of target proteins is believed to be a fundamental mechanism that underlies H2S-regulated signaling pathways. Cysteine S-Persulfidation is an important paradigm of post translational protein modification in the process of H2S signaling. This model is established as a critical redox mechanism to regulate numerous biological functions, especially in H2S-mediated neuroprotection and neurogenesis. Although the current research of S-Persulfidation is still in its infancy, accumulative evidence suggests that protein S-Persulfidation may share similar characteristics with protein S-nitrosylation. In this review, we will provide a comprehensive insight into the S-Persulfidation biology of H2S and polysulfides in neurological ailments and presume potential avenues for therapeutic development in these disorders based on S-Persulfidation of target proteins.
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Expanding the molecular spectrum and the neurological phenotype related to CAMTA1 variants.
Jacobs, EZ, Brown, K, Byler, MC, D'haenens, E, Dheedene, A, Henderson, LB, Humberson, JB, van Jaarsveld, RH, Kanani, F, Lebel, RR, et al
Clinical genetics. 2021;(2):259-268
Abstract
The CAMTA1-associated phenotype was initially defined in patients with intragenic deletions and duplications who showed nonprogressive congenital ataxia, with or without intellectual disability. Here, we describe 10 individuals with CAMTA1 variants: nine previously unreported (likely) pathogenic variants comprising one missense, four frameshift and four nonsense variants, and one missense variant of unknown significance. Six patients were diagnosed following whole exome sequencing and four individuals with exome-based targeted panel analysis. Most of them present with developmental delay, manifesting in speech and motor delay. Other frequent findings are hypotonia, cognitive impairment, cerebellar dysfunction, oculomotor abnormalities, and behavioral problems. Feeding problems occur more frequently than previously observed. In addition, we present a systematic review of 19 previously published individuals with causal variants, including copy number, truncating, and missense variants. We note a tendency of more severe cognitive impairment and recurrent dysmorphic features in individuals with a copy number variant. Pathogenic variants are predominantly observed in and near the N- and C- terminal functional domains. Clinical heterogeneity is observed, but 3'-terminal variants seem to associate with less pronounced cerebellar dysfunction.
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αB-crystallin as a promising target in pathological conditions - A review.
Maksimiuk, M, Sobiborowicz, A, Tuzimek, A, Deptała, A, Czerw, A, Badowska-Kozakiewicz, AM
Annals of agricultural and environmental medicine : AAEM. 2020;(3):326-334
Abstract
INTRODUCTION AND OBJECTIVE αB-crystallin belongs to the ubiquitous family of small heat-shock proteins. It was discovered as a physiological protein of the eye lens, maintaining its liquid-like property. Furthermore, αB-crystallin was proved to playa bipolar role in both physiological and pathophysiological conditions. This review discusses current knowledge about the biology and genetics of αB-crystallin, and summarizes recent advances in understanding its role in ophthalmic and neurological disorders, as well as breast cancer, renal cancer and other malignancies. STATE OF KNOWLEDGE α-crystallins are established as important elements of the protein quality control network, and consequently their defects are related to multiple human diseases. New studies highlight αB-crystallin's involvement in proliferative diabetic retinopathy angiogenesis and point out its therapeutic potential in age-related macular degeneration. αB-crystallin is thought to be associated with the disease-causing protein aggregates, leading to its connection with such neurological disturbances as anaplastic astrocytoma, Parkinson disease, aging deficits in the peripheral nervous system and multiple sclerosis. In breast cancer, it was proven to be a marker of aggressive behaviur and cerebral metastases. Strong expression of αB-crystallin promoted growth and migration of clear cell renal cell carcinoma cells and was correlated with lower overall survival rate. Considering other malignancies, its various roles were established in colorectal and gastric cancers, head and neck squamous cell carcinomas and osteosarcomas. CONCLUSIONS Further studies concerning αB-crystallin seem to be enormously promising, as they might improve our understanding of common human pathologies as well as contemporary diagnostics and treatment.
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The neurological insights of the emerging coronaviruses.
Msigwa, SS, Wang, Y, Li, Y, Cheng, X
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2020;:1-7
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Abstract
Emerging Viral diseases are incredibly infectious and proficient in inducing pandemics. Unlike the previous emerging coronaviruses (ECoVs) which neurological complexities were uncommon, with neurological features exhibition at 14-25 days post-onset, yet with critical outcomes exhibiting >50% mortality in central nervous (CNS) presenting pathologies. The COVID 19 neurological consequences occur more frequently even in mild cases, presenting with CNS involvement in up to 25%, musculoskeletal and peripheral manifestation (PNM). Through preceding ECoVs case reports, the PNM not linked to fatal outcomes, however, required, repeated neuro-imaging as notable CT and MRI changes appeared as late as 21 days while the likelihood of Cerebrospinal fluid to test positive for ECoV was 25%, only in the CNS presenting cases. Owing to 44-60% myalgia presentation, risk of the high inflammatory state, and coagulation cascade abnormalities reported in ECoVs, testing for C-reactive protein, serum creatine kinase, and D-dimer level is mandatory. Presently, there is no antiviral medication or vaccination for the ECoVs, early induction of antiviral drugs remains the backbone of management. Neurologically, the therapeutic dosages of anticoagulants are linked to the high incidence of thrombotic complexities, while methylprednisolone is associated with myopathy. Future studies expected to apply more neuro-imaging techniques for CNS exploration and further explore the pathogenesis of the COVID 19 myalgia, anosmia/ageusia reported in the majority of the initial cases.