Neurological disorders significantly impact the central nervous system, contributing to a growing public health crisis globally. The spectrum of these disorders includes neurodevelopmental and neurodegenerative diseases. This manuscript reviews the crucial roles of cellular signalling pathways in the pathophysiology of these conditions, focusing primarily on glutaminase/glutamate/NMDA receptor signalling, alongside the mitogen-activated protein kinase (MAPK) pathways-ERK1/2, C-JNK, and P38 MAPK. Activation of these pathways is often correlated with neuronal excitotoxicity, apoptosis, and inflammation, leading to many other pathological conditions such as traumatic brain injury, stroke, and brain tumor. The interplay between glutamate overstimulation and MAPK signalling exacerbates neurodegenerative processes, underscoring the complexity of cellular communication in maintaining neuronal health. Dysfunctional signalling alters synaptic plasticity and neuronal survival, contributing to cognitive impairments in various neurological diseases. The manuscript emphasizes the potential of targeting these signalling pathways for therapeutic interventions, promoting neuroprotection and reducing neuroinflammation. Incorporating insights from precision medicine and innovative drug delivery systems could enhance treatment efficacy. Overall, understanding the intricate mechanisms of these pathways is essential for developing effective strategies to mitigate the impact of neurological disorders and improve patient outcomes. This review highlights the necessity for further exploration into these signalling cascades to facilitate advancements in therapeutic approaches, ensuring better prognoses for individuals affected by neurological conditions.
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http://dx.doi.org/10.1016/j.neuroscience.2025.01.021 | DOI Listing |
J Neuroinflammation
January 2025
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice.
View Article and Find Full Text PDFEur J Med Res
January 2025
Clinical Research and Big Data Center, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
Objectives: Poststroke dysphagia (PSD) is a common complication after stroke but there is limited information on its global prevalence and influencing factors, such as spatial, temporal, demographic characteristics, and stroke-related factors. Our study seeks to fill this knowledge gap by exploring the overall prevalence of PSD and its influencing factors.
Methods: A search of English-language literature from database inception from 2005 until May 2022 was performed using PubMed, Embase, Web of Science, Cochrane Library, and Scopus.
BMC Med Genomics
January 2025
Department of Otolaryngology, First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, WuHua District, Kunming City, Yunnan Province, China.
Hearing loss is a prevalent condition with a significant impact on individuals' quality of life. However, comprehensive studies investigating the differential gene expression and regulatory mechanisms associated with hearing loss are lacking, particularly in the context of diverse patient samples. In this study, we integrated data from 10 patients across different regions, age groups, and genders, with their data retrieved from a public transcriptome database, to explore the molecular basis of hearing loss.
View Article and Find Full Text PDFEur J Med Res
January 2025
Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Background: To investigate the alterations in spontaneous brain activity and the similarities and differences between monocular deprivation amblyopia and binocular deprivation amblyopia.
Methods: Twenty children with binocular deprivation amblyopia, 26 children with monocular deprivation amblyopia and 20 healthy controls underwent resting-state functional magnetic resonance imaging. The evaluation of altered spontaneous brain activity was conducted using fractional amplitude of low-frequency fluctuations (fALFF).
Mol Brain
January 2025
Graduate Program in Neuroscience, University of Washington, Seattle, WA, 98195, USA.
Recent research has highlighted widespread dysregulation of alternative polyadenylation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Here, we identify significant disruptions to 3` UTR polyadenylation in the ALS/FTLD-TDP mouse model rNLS8 that correlate with changes in gene expression and protein levels through the re-analysis of published RNA sequencing and proteomic data. A subset of these changes are shared with TDP-43 knock-down mice suggesting depletion of endogenous mouse TDP-43 is a contributor to polyadenylation dysfunction in rNLS8 mice.
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