Special Issue "Therapeutic Agents for Neurological Disorders"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 31 December 2020.

Special Issue Editor

Dr. Damian Holsinger
Website
Guest Editor
Discipline of Pathology, Faculty of Medicine and Health, The University of Sydney, NSW, Australia
Interests: neurodegenerative diseases, Alzheimer’s disease, dementia, cell biology, molecular biology, ageing

Special Issue Information

Dear Colleagues,

The World Health Organization defines neurological disorders as disabling conditions that encompass but are not limited to cerebrovascular diseases, epilepsy, dementias including Alzheimer’s, multiple sclerosis, movement disorders resulting from nervous system deficits, brain tumours, neuroinfections and neurological disorders as a result of malnutrition 1. Globally, in 2016, neurological disorders were the leading cause of disability-adjusted life years (DALYs) (276 million [95% UI 247–308]) and second leading cause of deaths (9.0 million [8.8–9.4]) 2. The absolute number of deaths and DALYs from all neurological disorders combined increased by 39% and 15% respectively2. These figures outline an impending epidemic that requires urgent attention.

Treatments for neurological disorders are challenging, but numerous advancements have been made in identifying mechanisms and delineating pathways underlying these diseases. Advances in technologies that garner information from the fields of bioinformatics and next generation and whole genome sequencing have added invaluable support in identifying ‘culprit’ genes and proteins. Using this information, scientists and clinicians have ventured into areas previously deemed ‘fiction.’ From brain-controlled, non-invasive muscle stimulators that help paraplegics walk to the editing of the CEP290 gene in individuals with Leber congenital amaurosis 10 (LCA10) and a plethora of therapies in between, biomedicine has made giant leaps in just over two decades.

In this Special Issue, we aim to draw together research from experts in the field that highlight therapeutic agents and strategies, and identify future directions that will lead to discoveries and therapies for neurological disorders.

Dr. Damian Holsinger
Guest Editor

  1. http://www.who.int/features/qa/55/en
  2. GBD 2016 Neurology Collaborators (2019) Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 18: 459–80.

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Keywords

  • neurodegeneration
  • brain injury
  • spinal cord injury
  • neurodevelopmental disorders
  • nerve repair
  • brain tumors
  • neuromodulation
  • neuroinflammation

Published Papers (2 papers)

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Research

Open AccessArticle
Upregulated and Hyperactivated Thalamic Connexin 43 Plays Important Roles in Pathomechanisms of Cognitive Impairment and Seizure of Autosomal Dominant Sleep-Related Hypermotor Epilepsy with S284L-Mutant α4 Subunit of Nicotinic ACh Receptor
Pharmaceuticals 2020, 13(5), 99; https://doi.org/10.3390/ph13050099 - 18 May 2020
Abstract
To understand the pathomechanism and pathophysiology of autosomal dominant sleep-related hypermotor epilepsy (ADSHE), we studied functional abnormalities of glutamatergic transmission in thalamocortical pathway from reticular thalamic nucleus (RTN), mediodorsal thalamic nucleus (MDTN) to orbitofrontal cortex (OFC) associated with S286L-mutant α4β2-nicotinic acetylcholine receptor (nAChR), [...] Read more.
To understand the pathomechanism and pathophysiology of autosomal dominant sleep-related hypermotor epilepsy (ADSHE), we studied functional abnormalities of glutamatergic transmission in thalamocortical pathway from reticular thalamic nucleus (RTN), mediodorsal thalamic nucleus (MDTN) to orbitofrontal cortex (OFC) associated with S286L-mutant α4β2-nicotinic acetylcholine receptor (nAChR), and connexin43 (Cx43) hemichannel of transgenic rats bearing rat S286L-mutant Chrna4 gene (S286L-TG), corresponding to the human S284L-mutant CHRNA4 gene using simple Western analysis and multiprobe microdialysis. Cx43 expression in the thalamic plasma membrane fraction of S286L-TG was upregulated compared with that of wild-type. Subchronic administrations of therapeutic-relevant doses of zonisamide (ZNS) and carbamazepine (CBZ) decreased and did not affect Cx43 expression of S286L-TG, respectively. Upregulated Cx43 enhanced glutamatergic transmission during both resting and hyperexcitable stages in S286L-TG. Furthermore, activation of GABAergic transmission RTN–MDTN pathway conversely enhanced, but not inhibited, l-glutamate release in the MDTN via upregulated/activated Cx43. Local administration of therapeutic-relevant concentration of ZNS and CBZ acutely supressed and did not affect glutamatergic transmission in the thalamocortical pathway, respectively. These results suggest that pathomechanisms of ADSHE seizure and its cognitive deficit comorbidity, as well as pathophysiology of CBZ-resistant/ZNS-sensitive ADSHE seizures of patients with S284L-mutation. Full article
(This article belongs to the Special Issue Therapeutic Agents for Neurological Disorders)
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Open AccessArticle
Upregulated Connexin 43 Induced by Loss-of-Functional S284L-Mutant α4 Subunit of Nicotinic ACh Receptor Contributes to Pathomechanisms of Autosomal Dominant Sleep-Related Hypermotor Epilepsy
Pharmaceuticals 2020, 13(4), 58; https://doi.org/10.3390/ph13040058 - 29 Mar 2020
Cited by 1
Abstract
To study the pathomechanism and pathophysiology of autosomal dominant sleep-related hypermotor epilepsy (ADSHE), this study determined functional abnormalities of glutamatergic transmission in the thalamocortical motor pathway, from the reticular thalamic nucleus (RTN), motor thalamic nuclei (MoTN) tosecondary motor cortex (M2C) associated with the [...] Read more.
To study the pathomechanism and pathophysiology of autosomal dominant sleep-related hypermotor epilepsy (ADSHE), this study determined functional abnormalities of glutamatergic transmission in the thalamocortical motor pathway, from the reticular thalamic nucleus (RTN), motor thalamic nuclei (MoTN) tosecondary motor cortex (M2C) associated with the S286L-mutant α4β2-nicotinic acetylcholine receptor (nAChR) and the connexin43 (Cx43) hemichannel of transgenic rats bearing the rat S286L-mutant Chrna4 gene (S286L-TG), which corresponds to the human S284L-mutant CHRNA4 gene using multiprobe microdialysis, primary cultured astrocytes and a Simple Western system. Expression of Cx43 in the M2C plasma membrane fraction of S286L-TG was upregulated compared with wild-type rats. Subchronic nicotine administration decreased Cx43 expression of wild-type, but did not affect that of S286L-TG; however, zonisamide (ZNS) decreased Cx43 in both wild-type and S286L-TG. Primary cultured astrocytes of wild-type were not affected by subchronic administration of nicotine but was decreased by ZNS. Upregulated Cx43 enhanced glutamatergic transmission during both resting and hyperexcitable stages in S286L-TG. Furthermore, activation of glutamatergic transmission associated with upregulated Cx43 reinforced the prolonged Cx43 hemichannel activation. Subchronic administration of therapeutic-relevant doses of ZNS compensated the upregulation of Cx43 and prolonged reinforced activation of Cx43 hemichannel induced by physiological hyperexcitability during the non-rapid eye movement phase of sleep. The present results support the primary pathomechanisms and secondary pathophysiology of ADSHE seizures of patients with S284L-mutation. Full article
(This article belongs to the Special Issue Therapeutic Agents for Neurological Disorders)
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