CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 20, Issue 7, 2021

Background: The objective of the present review is to perform the 1st bibliometric analysis of sleep disorders research. Methods: The data was retrieved from Scopus in July 2020 for detailed analysis. Results: The 1st precise document about the sleep disorder was published in 1945. Till 15th July 2020, a total of 69657 documents were found in the Scopus database. Approximately eighty-two percent (57013/81.87%) of documents are published in the last twenty years (from 2001-2020). We calculated the per-year Growth Rate (GR) of publications (from 2000-onwards). The highest number of documents are published in 2019 (4337/7.90% of 57013) followed by 2018 (4249/7.74% of 57013) and 2017 (3974/7.24% of 57013). The productivity index (PI) for 1950-1960 and 2011-2020 era was found to be 100.21. We also provided the details of the top 50 countries with the maximum number of publications (from 1945 to July 2020). The top three (3) countries are the USA, with 24262 publications (34.83%), followed by UK (5566/8.0%) and Germany (4791/6.87%). We also performed the co-words analysis. Total 956643 (0.95 million) keywords were retrieved from 69657 published documents. After a critical analysis, we categorized them into different groups to show the trend in various domains. In the next phase of the study, only those documents were analyzed, which contained the phrase “sleep disorder” in the titles of the publications. Total 3626 documents were found. We calculated the per-year growth rate (GR). The continental distribution, the list of top twenty authors, sources/journals, departments or institutes, countries and research documents with highest citations are provided. By VOS viewer analysis, 6752, 36511 and 11473 terms in titles of the manuscripts, abstracts, and keywords were recorded, respectively. This may help in describing the overall trend in these publications. Conclusions: The present study provides a detailed list of top authors, departments, countries, sources, and top 20 most cited documents. The co-words analysis may help in describing the trends in the field of sleep disorders.

Sleep disorders have been shown to increase the risk of dementia. This particular aspect may affect the cognition of the patient, leading to behavioral disorders and depression. In early symptomatic Alzheimer’s Disease (AD), Default Mode Network (DMN) disruption occurs and progresses along with the course of the disease. This review mainly focuses on the leading causes of AD along with management of conditions like insomnia, obstructive sleep apnea, night-time sleep duration, Circadian Rhythm Disorder (CRD), neuroendocrine alternation, and impaired sleep to prevent the use of drugs that can cause complications, especially falls or additional cognitive deficits. Moreover, this study highlights the identification of molecular mechanisms like the effect of impaired sleep on amyloid β (Aβ) and tau dynamics, impaired proteostasis, along with appropriate measures to treat few contributing factors that lead to insomnia in AD or Mild Cognitive Impairment (MCI).

Dementia and diabetes are the two major disorders that are linked at both biochemical and molecular levels, which is due to the existing similarities between pancreatic beta-cells and neuronal cells at the transcriptional and translational levels. Both diseases have similar causative genes or factors, and dementia is one of the advanced complications in about 50-52% of patients with Type 2 Diabetes Mellitus (T2DM). Further, patients with T2DM are at a higher risk of neuronal degeneration and Alzheimer’s Disease (AD). Dementia, which is most common in AD, is associated with diminished insulin receptors by nearly 80%. The impairment in insulin signaling thus leads to the development of dementia and AD. Biochemical changes in ‘tau’ protein and amyloid-- beta proteins make them critical players in the formation of plaques in patients with dementia and AD. Here, we decode various cellular and molecular mechanisms associated with the development of dementia in patients with diabetes and AD.

A proteome is defined as a comprehensive protein set either of an organ or an organism at a given time and under specific physiological conditions. Accordingly, the study of the nervous system’s proteomes is called neuroproteomics. In the neuroproteomics process, various pieces of the nervous system are “fragmented” to understand the dynamics of each given sub-proteome in a much better way. Functional proteomics addresses the organisation of proteins into complexes and the formation of organelles from these multiprotein complexes that control various physiological processes. Current functional studies of neuroproteomics mainly talk about the synapse structure and its organisation, the major building site of the neuronal communication channel. The proteomes of synaptic vesicle, presynaptic terminal, and postsynaptic density, have been examined by various proteomics techniques. The objectives of functional neuroproteomics are: to solve the proteome of single neurons or astrocytes grown in cell cultures or from the primary brain cells isolated from tissues under various conditions, to identify the set of proteins that characterize specific pathogenesis, or to determine the group of proteins making up postsynaptic or presynaptic densities. It is usual to solve a particular sub-proteome like the heat-shock response proteome or the proteome responding to inflammation. Post-translational protein modifications alter their functions and interactions. The techniques to detect synapse phosphoproteome are available. However, techniques for the analysis of ubiquitination and sumoylation are under development.

Neuroblastoma (NBM) is the second leading pediatric cancer that develops from the precursors of the sympathetic nervous system. To date, surgery, chemotherapy, and radiation serve as the first-line treatment against NBM in high-risk patients. However, few of these approaches have severe side effects. Recently, numerous studies have also reported that high chemotherapy doses, along with stem cell rescue, improvise event-free survival in patients. In this review, the authors attempted to discuss the pathogenesis associated with NBM and how stem cell therapy can be employed for the treatment of NBM. Stem cells are a group of multipotent, undifferentiated cells that are capable of producing all cells in a particular tissue, organ, or organism. They have an endogenous self-renewal property. This property is tightly modulated for the normal homeostasis within the body. However, the failure of this process leads to carcinogenesis, including NBM. As these properties are modulated via various intrinsic as well as extrinsic pathways, the arrest of these pathways via various drugs may help in controlling various carcinomas, including NBM. Recently, stem cells were utilized for the diagnosis and treatment of NBM. Nevertheless, most of the studies conducted to date are mainly designed on bulk-cell analysis, which in turn provides little information about the population of cells. Thus, the authors believe that, by employing single-cell RNA sequencing technologies and computational approaches, we can unmask the tumor heterogeneity in NBM in a more comprehensive way. In the near future, this information will be highly useful for the identification of biomarkers and treatment associated with NBM in humans.

Epilepsy responds to pharmacotherapy in its initial stages. The response of some forms of epilepsy, like the refractory epilepsy, is extremely low. Surgical management of epilepsy is associated with complications, which necessitates the search for novel and modern strategies for the treatment of epilepsy. Neuroprotection and neuronal regeneration are the major targets that must be accomplished by the new strategies. Hematopoietic Stem Cell (HSCs) therapy for epilepsy has shown promising results in pre-clinical studies with marginal clinical effects. This review explores the characteristics, mechanism of action, and clinical significance of HSCs therapy for the treatment of epilepsy.

Vascular Dementia (VaD) occurs due to cerebrovascular insufficiency, which leads to decreased blood circulation to the brain, thereby resulting in mental disabilities. The main causes of Vascular Cognitive Impairment (VCI) are severe hypoperfusion, stroke, hypertension, large vessel disease (cortical), small Vessel Disease (subcortical VaD), strategic infarct, hemorrhage (microbleed), Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), and Cerebral Amyloid Angiopathy (CAA), which leads to decreased cerebrovascular perfusion. Many metabolic disorders such as Diabetes Mellitus (DM), dyslipidemia, and hyperhomocysteinemia are also related to VaD. The rodent experimental models provide a better prospective for the investigation of the molecular mechanism of new drugs. A plethora of experimental models are available that mimic the pathological conditions and lead to VaD. This review article updates the current knowledge on the basis of VaD, risk factors, pathophysiology, mechanism, advantages, limitations, and the modification of various available rodent experimental models.