Signaling Biomolecules in the Central Nervous System (CNS)—At the Nexus of Neuropsychiatric and Neurodegenerative Disorders

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 October 2022) | Viewed by 21695

Special Issue Editors

Department of Brain Biochemistry, Maj Institute of Pharmacology of the Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland
Interests: neuroscience; neuropharmacology; stress-related disorders; depression; psychotropic drugs; GPCR signaling; noradrenergic system; neuroplasticity
Special Issues, Collections and Topics in MDPI journals
Department of Brain Biochemistry, Maj Institute of Pharmacology of the Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland
Interests: neuropharmacology; neuroplasticity; neurotrophic factors; gene therapy; high content image analysis; alpha-synuclein; noradrenergic system; neurodegenerative disorders; stress-related disroders
Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland
Interests: dopamine system; neuroprotection; neurotrophic factors; Parkinson's disease; stroke; stem cells; proteostasis

Special Issue Information

Dear Colleagues,

Signaling biomolecules are central to the transmission of information between cells and as such, are critical to the integrity of the organism and particularly important to the function of Central Nervous System (CNS). Consequently, they are also implicated in virtually all CNS disorders. Classical neurotransmitters, neuropeptides, neurotrophic factors and multiple peripherally released peptide hormones like insulin, ghrelin, irisin, or leptin all act as signaling biomolecules in CNS. Signaling biomolecules most often act as ligands for specific receptors, either membrane-bound or intracellular. However, single signaling biomolecule frequently has multiple known receptors of different functions, and even the same receptor can act differently in different cellular populations. Not surprisingly, a single signaling biomolecule is often known to play important roles in classically distinct ailments. Moreover, with improved diagnostics and advancement in clinical care, it’s becoming apparent that comorbidity in CNS disorders is the norm rather than the exception.

This special issue welcomes all work relating to signaling biomolecules in neuropsychiatric, neurodegenerative and other CNS disorders, focusing on their role in either pathophysiology or treatments. Especially original research papers investigating roles of specific molecules in comorbid disorders or role in interplay between different CNS disorders and review papers describing diverse roles and therapeutic potential of a specific molecule and their receptor system are encouraged for submission. More narrowly focused research papers are also welcome but they are encouraged to discuss their findings from potential importance to multiple disorders.

Prof. Dr. Irena Nalepa
Dr. Piotr Chmielarz
Prof. Dr. Mikko Airavaara
Guest Editors

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Keywords

  • mood and anxiety disorders
  • Parkinson’s disease
  • mechanisms of neurodegeneration
  • neuroprotection and brain repair
  • animal models
  • neurotransmitters
  • G protein-coupled receptors (GPCR)
  • protein kinases
  • receptor– (RTK) and non–receptor tyrosine kinases
  • trophic factors
  • neuroplasticity

Published Papers (7 papers)

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Research

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28 pages, 2622 KiB  
Article
Gene Expression Changes Induced by Exposure of RAW 264.7 Macrophages to Particulate Matter of Air Pollution: The Role of Endotoxins
by Adam Roman, Michał Korostyński, Monika Jankowska-Kieltyka, Marcin Piechota, Jacek Hajto and Irena Nalepa
Biomolecules 2022, 12(8), 1100; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12081100 - 10 Aug 2022
Viewed by 1909
Abstract
Despite the variable chemical and physical characteristics of particulate air pollutants, inflammation and oxidative stress have been identified as common mechanisms for cell damage and negative health influences. These effects are produced by organic components, especially by endotoxins. This study analyzed the gene [...] Read more.
Despite the variable chemical and physical characteristics of particulate air pollutants, inflammation and oxidative stress have been identified as common mechanisms for cell damage and negative health influences. These effects are produced by organic components, especially by endotoxins. This study analyzed the gene expression profile after exposure of RAW 264.7 cells to the standard particulate matter (PM) material, NIST1648a, and PM with a reduced organic matter content, LAp120, in comparison to the effects of lipopolysaccharide (LPS). The selected parameters of cell viability, cell cycle progression, and metabolic and inflammatory activity were also investigated. Both forms of PM negatively influenced the parameters of cell activity. These results were generally reflected in the gene expression profile. Only NIST1648a, excluding LAp120, contained endotoxins and showed small but statistically significant pro-inflammatory activity. However, the gene expression profiling revealed strong pro-inflammatory cell activation induced by NIST1648a that was close to the effects of LPS. Changes in gene expression triggered by LAp120 were relatively small. The observed differences in the effects of NIST1648a and LAp120 were related to the content of organic matter in which bacterial endotoxins play an important role. However, other organic compounds and their interactions with other PM components also appear to be of significant importance. Full article
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15 pages, 4421 KiB  
Article
Cell Culture Media, Unlike the Presence of Insulin, Affect α-Synuclein Aggregation in Dopaminergic Neurons
by Irena Hlushchuk, Justyna Barut, Mikko Airavaara, Kelvin Luk, Andrii Domanskyi and Piotr Chmielarz
Biomolecules 2022, 12(4), 563; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12040563 - 09 Apr 2022
Cited by 3 | Viewed by 3451
Abstract
There are several links between insulin resistance and neurodegenerative disorders such as Parkinson’s disease. However, the direct influence of insulin signaling on abnormal α-synuclein accumulation—a hallmark of Parkinson’s disease—remains poorly explored. To our best knowledge, this work is the first attempt to investigate [...] Read more.
There are several links between insulin resistance and neurodegenerative disorders such as Parkinson’s disease. However, the direct influence of insulin signaling on abnormal α-synuclein accumulation—a hallmark of Parkinson’s disease—remains poorly explored. To our best knowledge, this work is the first attempt to investigate the direct effects of insulin signaling on pathological α-synuclein accumulation induced by the addition of α-synuclein preformed fibrils in primary dopaminergic neurons. We found that modifying insulin signaling through (1) insulin receptor inhibitor GSK1904529A, (2) SHIP2 inhibitor AS1949490 or (3) PTEN inhibitor VO-OHpic failed to significantly affect α-synuclein aggregation in dopaminergic neurons, in contrast to the aggregation-reducing effects observed after the addition of glial cell line-derived neurotrophic factor. Subsequently, we tested different media formulations, with and without insulin. Again, removal of insulin from cell culturing media showed no effect on α-synuclein accumulation. We observed, however, a reduced α-synuclein aggregation in neurons cultured in neurobasal medium with a B27 supplement, regardless of the presence of insulin, in contrast to DMEM/F12 medium with an N2 supplement. The effects of culture conditions were present only in dopaminergic but not in primary cortical or hippocampal cells, indicating the unique sensitivity of the former. Altogether, our data contravene the direct involvement of insulin signaling in the modulation of α-synuclein aggregation in dopamine neurons. Moreover, we show that the choice of culturing media can significantly affect preformed fibril-induced α-synuclein phosphorylation in a primary dopaminergic cell culture. Full article
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16 pages, 5376 KiB  
Article
The MAP Kinase Phosphatase MKP-1 Modulates Neurogenesis via Effects on BNIP3 and Autophagy
by Yinghui Li and Marc W. Halterman
Biomolecules 2021, 11(12), 1871; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11121871 - 14 Dec 2021
Cited by 3 | Viewed by 2310
Abstract
Inherited and acquired defects in neurogenesis contribute to neurodevelopmental disorders, dysfunctional neural plasticity, and may underlie pathology in a range of neurodegenerative conditions. Mitogen-activated protein kinases (MAPKs) regulate the proliferation, survival, and differentiation of neural stem cells. While the balance between MAPKs and [...] Read more.
Inherited and acquired defects in neurogenesis contribute to neurodevelopmental disorders, dysfunctional neural plasticity, and may underlie pathology in a range of neurodegenerative conditions. Mitogen-activated protein kinases (MAPKs) regulate the proliferation, survival, and differentiation of neural stem cells. While the balance between MAPKs and the family of MAPK dual-specificity phosphatases (DUSPs) regulates axon branching and synaptic plasticity, the specific role that DUSPs play in neurogenesis remains unexplored. In the current study, we asked whether the canonical DUSP, MAP Kinase Phosphatase-1 (MKP-1), influences neural stem cell differentiation and the extent to which DUSP-dependent autophagy is operational in this context. Under basal conditions, Mkp-1 knockout mice generated fewer doublecortin (DCX) positive neurons within the dentate gyrus (DG) characterized by the accumulation of LC3 puncta. Analyses of wild-type neural stem cell (NSC) differentiation in vitro revealed increased Mkp-1 mRNA expression during the initial 24-h period. Notably, Mkp-1 KO NSC differentiation produced fewer Tuj1-positive neurons and was associated with increased expression of the BCL2/adenovirus E1B 19-kD protein-interacting protein 3 (BNIP3) and levels of autophagy. Conversely, Bnip3 knockdown in differentiated Mkp-1 KO NSCs reduced levels of autophagy and increased neuronal yields. These results indicate that MKP-1 exerts a pro-neurogenic bias during a critical window in NSC differentiation by regulating BNIP3 and basal autophagy levels. Full article
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9 pages, 2183 KiB  
Article
Blood-Derived α-Synuclein Aggregated in the Substantia Nigra of Parabiotic Mice
by Xizhen Ma, Leilei Chen, Ning Song, Le Qu, Jun Wang and Junxia Xie
Biomolecules 2021, 11(9), 1287; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11091287 - 29 Aug 2021
Cited by 1 | Viewed by 1997
Abstract
As a pathological biomarker of Parkinson’s disease, α-synuclein is thought to be a prion-like protein, but evidence for the transmission of α-synuclein from blood to the brain is unclear. The goals of this study were to determine whether blood-derived α-synuclein could enter the [...] Read more.
As a pathological biomarker of Parkinson’s disease, α-synuclein is thought to be a prion-like protein, but evidence for the transmission of α-synuclein from blood to the brain is unclear. The goals of this study were to determine whether blood-derived α-synuclein could enter the brains of mice and whether α-synuclein in the brain could be cleared by parabiosis. Heterochronic parabiosis was performed on SNCAA53T transgenic mice (A53T mice) and wildtype mice. The levels of human α-synuclein in the blood and substantia nigra of wildtype mice were significantly increased after 4-month parabiosis with A53T mice. Moreover, the expression of α-synuclein filament, but not of total α-synuclein, was significantly increased in the substantia nigra of wildtype mice that were paired with A53T mice. However, the levels of human α-synuclein displayed no significant change in the serum, blood, or substantia nigra of A53T mice. These results provide direct evidence that pathological α-synuclein can be transmitted from blood to the brain in the heterochronic parabiosis system; however, it appears to be difficult to clear it from the brain in a short period of time. Full article
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Review

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20 pages, 752 KiB  
Review
Effect of Cannabis on Memory Consolidation, Learning and Retrieval and Its Current Legal Status in India: A Review
by Nandi Niloy, Tousif Ahmed Hediyal, Chandrasekaran Vichitra, Sharma Sonali, Saravana Babu Chidambaram, Vasavi Rakesh Gorantla and Arehally M. Mahalakshmi
Biomolecules 2023, 13(1), 162; https://0-doi-org.brum.beds.ac.uk/10.3390/biom13010162 - 12 Jan 2023
Cited by 3 | Viewed by 4208
Abstract
Cannabis is one of the oldest crops grown, traditionally held religious attachments in various cultures for its medicinal use much before its introduction to Western medicine. Multiple preclinical and clinical investigations have explored the beneficial effects of cannabis in various neurocognitive and neurodegenerative [...] Read more.
Cannabis is one of the oldest crops grown, traditionally held religious attachments in various cultures for its medicinal use much before its introduction to Western medicine. Multiple preclinical and clinical investigations have explored the beneficial effects of cannabis in various neurocognitive and neurodegenerative diseases affecting the cognitive domains. Tetrahydrocannabinol (THC), the major psychoactive component, is responsible for cognition-related deficits, while cannabidiol (CBD), a non-psychoactive phytocannabinoid, has been shown to elicit neuroprotective activity. In the present integrative review, the authors focus on the effects of cannabis on the different cognitive domains, including learning, consolidation, and retrieval. The present study is the first attempt in which significant focus has been imparted on all three aspects of cognition, thus linking to its usage. Furthermore, the investigators have also depicted the current legal position of cannabis in India and the requirement for reforms. Full article
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20 pages, 5119 KiB  
Review
Sexual Dimorphism in Neurodegenerative Diseases and in Brain Ischemia
by Teresa Zalewska, Paulina Pawelec, Karolina Ziabska and Malgorzata Ziemka-Nalecz
Biomolecules 2023, 13(1), 26; https://0-doi-org.brum.beds.ac.uk/10.3390/biom13010026 - 22 Dec 2022
Cited by 6 | Viewed by 2467
Abstract
Epidemiological studies and clinical observations show evidence of sexual dimorphism in brain responses to several neurological conditions. It is suggested that sex-related differences between men and women may have profound effects on disease susceptibility, pathophysiology, and progression. Sexual differences of the brain are [...] Read more.
Epidemiological studies and clinical observations show evidence of sexual dimorphism in brain responses to several neurological conditions. It is suggested that sex-related differences between men and women may have profound effects on disease susceptibility, pathophysiology, and progression. Sexual differences of the brain are achieved through the complex interplay of several factors contributing to this phenomenon, such as sex hormones, as well as genetic and epigenetic differences. Despite recent advances, the precise link between these factors and brain disorders is incompletely understood. This review aims to briefly outline the most relevant aspects that differ between men and women in ischemia and neurodegenerative disorders (AD, PD, HD, ALS, and SM). Recognition of disparities between both sexes could aid the development of individual approaches to ameliorate or slow the progression of intractable disorders. Full article
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17 pages, 1208 KiB  
Review
Somatostatin and Somatostatin-Containing Interneurons—From Plasticity to Pathology
by Monika Liguz-Lecznar, Grzegorz Dobrzanski and Malgorzata Kossut
Biomolecules 2022, 12(2), 312; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12020312 - 15 Feb 2022
Cited by 9 | Viewed by 3723
Abstract
Despite the obvious differences in the pathophysiology of distinct neuropsychiatric diseases or neurodegenerative disorders, some of them share some general but pivotal mechanisms, one of which is the disruption of excitation/inhibition balance. Such an imbalance can be generated by changes in the inhibitory [...] Read more.
Despite the obvious differences in the pathophysiology of distinct neuropsychiatric diseases or neurodegenerative disorders, some of them share some general but pivotal mechanisms, one of which is the disruption of excitation/inhibition balance. Such an imbalance can be generated by changes in the inhibitory system, very often mediated by somatostatin-containing interneurons (SOM-INs). In physiology, this group of inhibitory interneurons, as well as somatostatin itself, profoundly shapes the brain activity, thus influencing the behavior and plasticity; however, the changes in the number, density and activity of SOM-INs or levels of somatostatin are found throughout many neuropsychiatric and neurological conditions, both in patients and animal models. Here, we (1) briefly describe the brain somatostatinergic system, characterizing the neuropeptide somatostatin itself, its receptors and functions, as well the physiology and circuitry of SOM-INs; and (2) summarize the effects of the activity of somatostatin and SOM-INs in both physiological brain processes and pathological brain conditions, focusing primarily on learning-induced plasticity and encompassing selected neuropsychological and neurodegenerative disorders, respectively. The presented data indicate the somatostatinergic-system-mediated inhibition as a substantial factor in the mechanisms of neuroplasticity, often disrupted in a plethora of brain pathologies. Full article
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