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Malignant tumors and central nervous system (CNS) disorders are intricately linked to a process known as ''aberrant cell cycle re-entry,'' which plays a critical role in the progression of these diseases. Addressing the dysregulation in cell cycles offers a promising therapeutic approach for cancers and CNS disorders. MicroRNAs (miRNAs) play a crucial role as regulators of gene expression in cell cycle transitions, presenting a promising therapeutic avenue for treating these disorders and their comorbidities. This review consolidates the progress made in the last three years regarding miRNA-based treatments for diseases associated with aberrant cell cycle re-entry. It encompasses exploring fundamental mechanisms and signaling pathways influenced by miRNAs in cancers and CNS disorders, particularly focusing on the therapeutic effects of exosome-derived miRNAs. The review also identifies specific miRNAs implicated in comorbidity of cancers and CNS disorders, discusses the future potential of miRNA reagents in managing cell cycle-related diseases.

Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords ''ATF4,'' ''Central Nervous System,'' ''Neurological,'' ''Alzheimer's disease,'' ''Parkinson's Disease,'' ''Stroke,'' ''Spinal Cord Injury,'' ''Glioblastoma,'' ''Traumatic Brain Injury,'' and ''Spinal Cord Injury.'' Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aβ, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.

Disorders of central nervous system (CNS) disorders are considered serious health issues. The most common CNS diseases include neurodegenerative diseases, mental disorders, demyelinating disease, ischemia-reperfusion injury, and neuroinflammation. As a natural phenolic compound, hesperidin is a flavanone glycoside with various biological effects. Increasing evidence show that the growth of CNS diseases is hindered by hesperidin. Here, we have reviewed the related literature on neuropharmacological mechanisms for the preventive and therapeutic effects of hesperidin on CNS diseases. Several cellular and animal models have been developed to evaluate the underlying neuropharmacological mechanisms of hesperidin. Additionally, clinical evidence has confirmed its neuroprotective function. Hesperidin exerts its neuroprotective properties by decreasing neuro-inflammatory and apoptotic pathways. Hesperidin function has been studied in preclinical models for CNS diseases, but little is known about its definite effect in humans. Hesperidin can effectively alleviate depression and improve cognition and memory. It is urgent to explore and discover clinical trials for further confirmation of the neuroprotective efficacy of hesperidin and to evaluate its safety profile.

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.

Chronic microglial activation is associated with the pathogenesis of several CNS disorders. Microglia show phenotypic diversity and functional complexity in diseased CNS. Thus, understanding the pathology-specific heterogeneity of microglial behavior is crucial for the future development of microglia-modulating therapy for variety of CNS disorders. This review summarizes up-to-date knowledge on how microglia contribute to CNS homeostasis during development and throughout adulthood. We discuss the heterogeneity of microglial phenotypes in the context of CNS disorders with an emphasis on neurodegenerative diseases, demyelinating diseases, CNS trauma, and epilepsy. We conclude this review with a discussion about the disease-specific heterogeneity of microglial function and how it could be exploited for therapeutic intervention.

The physical barrier between blood and the CNS (the blood–brain barrier, the blood–spinal cord barrier and the blood–CSF barrier) protects the CNS from both toxic and pathogenic agents in the blood. It is now clear that disruption of the blood–CNS barrier plays a key role in a number of CNS disorders, particularly those associated with neurodegeneration. Such disruption is inevitably accompanied by inflammatory change, as immune cells and immune mediators gain access to the brain or spinal cord. The blood–CNS barrier also presents a major obstacle for potential CNS medicines. Robust methods to assess CNS permeation are therefore essential for CNS drug discovery, particularly when brain pharmacokinetics are taken into account and especially when such measures are linked to neurochemical, physiological, behavioural or neuroimaging readouts of drug action. Drug candidates can be successfully designed to cross the blood–CNS barrier, but for those that can't there is the possibility of entry with a delivery system that facilitates the movement of drug candidate across the blood–CNS barrier.

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases., Competing Interests: The authors declare no conflicts of interest., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Central nervous system (CNS) disorders like Alzheimer's disease (AD), Parkinson disease (PD), stroke, epilepsy, depression, and bipolar disorder have a high impact on both medical and social problems due to the surge in their prevalence. All of these neuronal disorders share some common etiologies including disruption of Ca 2+ homeostasis and accumulation of misfolded proteins. These misfolded proteins further disrupt the intracellular Ca 2+ homeostasis by disrupting the activity of several ion channels including transient receptor potential (TRP) channels. TRP channel families include non-selective Ca 2+ permeable channels, which act as cellular sensors activated by various physio-chemical stimuli, exogenous, and endogenous ligands responsible for maintaining the intracellular Ca 2+ homeostasis. TRP channels are abundantly expressed in the neuronal cells and disturbance in their activity leads to various neuronal diseases. Under the pathological conditions when the activity of TRP channels is perturbed, there is a disruption of the neuronal homeostasis through increased inflammatory response, generation of reactive oxygen species, and mitochondrial dysfunction. Therefore, there is a potential of pharmacological interventions targeting TRP channels in CNS disorders. This review focuses on the role of TRP channels in neurological diseases; also, we have highlighted the current insights into the pharmacological modulators targeting TRP channels., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The limited efficiency of the current treatment options against the central nervous system (CNS) disorders has created increasing demands towards the development of novel theranostic strategies. The enormous research efforts in nanotechnology have led to the production of highly-advanced nanodevices and biomaterials in a variety of geometries and configurations for targeted delivery of genes, drugs, or growth factors across the blood-brain barrier. Meanwhile, the richness or reliability of data, drug delivery methods, therapeutic effects or potential toxicity of nanoparticles, occurrence of the unexpected phenomena due to the polydisperse or polymorphic nature of nanomaterials, and personalized theranostics have remained as challenging issues. In this respect, computational modelling has emerged as a powerful tool for rational design of nanoparticles with optimized characteristics including the selectivity, improved bioactivity, and reduced toxicity that might lead to the effective delivery of therapeutic agents. High-performance simulation techniques by shedding more light on the dynamical behaviour of neural networks and pathomechanisms of CNS disorders may provide imminent breakthroughs in nanomedicine. In the present review, the importance of integration of nanotechnology-based approaches with computational techniques for targeted delivery of theranostics to the CNS has been highlighted., (Copyright © 2017. Published by Elsevier Inc.)

Glutamate and γ-aminobutyric acid (GABA) are the major excitatory and inhibitory neurotransmitter systems, respectively in the central nervous system (CNS). Dysregulation, in any of these or both, has been implicated in various CNS disorders. GABA acts via ionotropic (GABA(A) and GABA(C) receptor) and metabotropic (GABA(B)) receptor. Dysregulation of GABAergic signaling and alteration in GABA(B) receptor expression has been implicated in various CNS disorders. Clinically, baclofen-a GABA(B) receptor agonist is available for the treatment of spasticity, dystonia etc., associated with various neurological disorders. Moreover, GABAB receptor ligands has also been suggested to be beneficial in various neuropsychiatric and neurodegenerative disorders. The present review is aimed to discuss the role of GABA(B) receptors and the possible outcomes of GABA(B) receptor modulation in CNS disorders., (© 2013.)