Montelukast improves disease outcome in SOD1G93A female mice by counteracting oligodendrocyte dysfunction and aberrant glial reactivity DOI Creative Commons
Stefano Raffaele, Nhung Nguyen, Marco Milanese

et al.

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 181(18), P. 3303 - 3326

Published: May 15, 2024

Abstract Background and Purpose Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss consequent muscle atrophy, for which no effective therapies are available. Recent findings reveal that disease progression fuelled early aberrant neuroinflammation the of oligodendrocytes with neuroprotective remyelinating properties. On this basis, pharmacological interventions capable restoring pro‐regenerative local milieu re‐establish proper oligodendrocyte functions may be beneficial. Experimental Approach Here, we evaluated in vivo therapeutic effects montelukast (MTK), an antagonist oligodendroglial G protein‐coupled receptor 17 (GPR17) cysteinyl‐leukotriene 1 (CysLT R) receptors on microglia astrocytes, SOD1 G93A ALS mouse model. We chronically treated mice MTK, starting from symptomatic stage. Disease was assessed behavioural immunohistochemical approaches. Key Results Oral MTK treatment significantly extended survival probability, delayed body weight ameliorated functionalityonly female mice. Noteworthy, restored maturation induced significant changes reactive phenotype morphological features microglia/macrophages astrocytes spinal cord mice, suggesting enhanced functions. Importantly, concomitant MN preservation has been detected after administration. No beneficial were observed male highlighting sex‐based difference protective activity MTK. Conclusions Implications Our results provide first preclinical evidence indicating repurposing safe marketed anti‐asthmatic drug, promising sex‐specific strategy personalized treatment.

Language: Английский

Energy metabolism in major depressive disorder: Recent advances from omics technologies and imaging DOI Open Access
Xinyi Gu,

Shuang Ke,

Qixue Wang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 141, P. 111869 - 111869

Published: July 2, 2021

Major depressive disorder (MDD) is a serious psychiatric that associated with high rate of disability and increasing suicide rate, the pathogenesis still unclear. Many researches showed energy metabolism patients depression impaired, which may be direction treatment. In this review, we focus on "omics" technologies such as genomics, proteomics, transcriptomics metabolomics, well imaging, progress MDD. These findings indicate abnormal one important mechanisms for occurrence development depression. Although research various ongoing, rapid new joint use will help to clarify explore efficient diagnosis treatment methods.

Language: Английский

Citations

65
The Emerging Role of Central and Peripheral Immune Systems in Neurodegenerative Diseases DOI Creative Commons

Xin Zang,

Si Chen, Junyao Zhu

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: April 25, 2022

For decades, it has been widely believed that the blood–brain barrier (BBB) provides an immune privileged environment in central nervous system (CNS) by blocking peripheral cells and humoral factors. This view revised recent years, with increasing evidence revealing plays a critical role regulating CNS homeostasis disease. Neurodegenerative diseases are characterized progressive dysfunction loss of neurons CNS. An number studies have focused on connection between neurodegenerative diseases. On one hand, peripherally released cytokines can cross BBB, cause direct neurotoxicity contribute to activation microglia astrocytes. other also infiltrate brain participate progression neuroinflammatory high morbidity disability rate, yet there no effective therapies stop or reverse their progression. In neuroinflammation received much attention as therapeutic target for many this review, we highlight emerging systems diseases, well interactions. A better understanding may improve strategies

Language: Английский

Citations

63
The Biogenesis of miRNAs and Their Role in the Development of Amyotrophic Lateral Sclerosis DOI Creative Commons
Jinmeng Liu, Fenghua Zhou, Yingjun Guan

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(3), P. 572 - 572

Published: Feb. 7, 2022

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects upper and lower motor neurons. As there no effective treatment for ALS, it particularly important to screen key gene therapy targets. The identifications of microRNAs (miRNAs) have completely changed the traditional view regulation. miRNAs are small noncoding single-stranded RNA molecules involved in regulation post-transcriptional expression. Recent advances also indicate biomarkers many diseases, including diseases. In this review, we summarize recent regarding mechanisms underlying role ALS pathogenesis its application ALS. potential target diverse pathways opens new avenue therapy.

Language: Английский

Citations

39
Oligodendrocyte progenitor cells in Alzheimer’s disease: from physiology to pathology DOI Creative Commons

Peibin Zou,

Chongyun Wu,

Timon Cheng‐Yi Liu

et al.

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: Nov. 14, 2023

Abstract Oligodendrocyte progenitor cells (OPCs) play pivotal roles in myelin formation and phagocytosis, communicating with neighboring contributing to the integrity of blood–brain barrier (BBB). However, under pathological circumstances Alzheimer’s disease (AD), brain’s microenvironment undergoes detrimental changes that significantly impact OPCs their functions. Starting OPC functions, we delve into transformation myelin-producing oligodendrocytes, intricate signaling interactions other central nervous system (CNS), fascinating process which influences function affects CNS homeostasis. Moreover, discuss essential role BBB highlight critical contribution forming CNS-protective barriers. In context AD, deterioration local brain is discussed, mainly focusing on neuroinflammation, oxidative stress, accumulation toxic proteins. The disturb delicate balance brain, impacting regenerative capacity compromising integrity. Under conditions, experience significant alterations migration proliferation, leading impaired differentiation a reduced ability produce mature oligodendrocytes. degeneration become increasingly active progressive neurodegeneration. Finally, summarize current therapeutic approaches targeting AD. Strategies revitalize senescence, modulate pathways enhance differentiation, explore potential avenues are promising alleviating AD function. conclusion, this review highlights indispensable involvement pathogenesis interplay between underscores complexity neurodegenerative diseases. Insights from studying conditions provide foundation for innovative strategies fostering Future research will advance our understanding management diseases, ultimately offering hope effective treatments improved quality life those affected by related disorders.

Language: Английский

Citations

24
Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis and Age-Related Neurodegeneration DOI Open Access
Frederick J. Arnold, Alexandra F. Putka,

Urmimala Raychaudhuri

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5587 - 5587

Published: May 21, 2024

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder. While there are five FDA-approved drugs for treating this disease, each has only modest benefits. To design new and more effective therapies ALS, particularly sporadic ALS of unknown diverse etiologies, we must identify key, convergent mechanisms disease pathogenesis. This review focuses on origin effects glutamate-mediated excitotoxicity in (the cortical hyperexcitability hypothesis), which increased glutamatergic signaling causes neurons to become hyperexcitable eventually die. We characterize both primary secondary contributions excitotoxicity, referring processes taking place at synapse within cell, respectively. ‘Primary pathways’ include upregulation calcium-permeable AMPA receptors, dysfunction EAAT2 astrocytic glutamate transporter, release from presynaptic terminal, reduced inhibition by interneurons—all have been observed patients model systems. ‘Secondary changes mitochondrial morphology function, production reactive oxygen species, endoplasmic reticulum (ER) stress. By identifying key targets cascade, emphasize importance pathway pathogenesis suggest that intervening could be developing disease.

Language: Английский

Citations

16
Astrocytes: Dissecting Their Diverse Roles in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia DOI Creative Commons
Chiara F. Valori,

Claudia Sulmona,

Liliana Brambilla

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(11), P. 1450 - 1450

Published: May 23, 2023

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders often co-occurring in the same patient, a feature that suggests common origin of two diseases. Consistently, pathological inclusions proteins as well mutations genes can be identified both ALS/FTD. Although many studies have described several disrupted pathways within neurons, glial cells also regarded crucial pathogenetic contributors Here, we focus our attention on astrocytes, heterogenous population perform functions for optimal central nervous system homeostasis. Firstly, discuss how post-mortem material from ALS/FTD patients supports astrocyte dysfunction around three pillars: neuroinflammation, abnormal protein aggregation, atrophy/degeneration. Furthermore, summarize current attempts at monitoring living using either novel imaging strategies or soluble biomarkers. We then address pathology is recapitulated animal cellular models used these to understand molecular mechanisms driving platforms pre-clinical testing therapeutics. Finally, present clinical trials ALS/FTD, restricting discussion treatments modulate functions, directly indirectly.

Language: Английский

Citations

19
Harnessing myelin water fraction as an imaging biomarker of human cerebral aging, neurodegenerative diseases, and risk factors influencing myelination: A review DOI Creative Commons

Mary E Faulkner,

Zhaoyuan Gong,

Alex Guo

et al.

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: July 8, 2024

Abstract Myelin water fraction (MWF) imaging has emerged as a promising magnetic resonance (MRI) biomarker for investigating brain function and composition. This comprehensive review synthesizes the current state of knowledge on MWF human cerebral aging, neurodegenerative diseases, risk factors influencing myelination. The databases used include Web Science, Scopus, Science Direct, PubMed. We begin with brief discussion theoretical foundations imaging, including its basis in MR physics mathematical modeling underlying calculation, an overview most adopted MRI methods imaging. Next, we delve into clinical research applications that have been explored to date, highlighting advantages limitations. Finally, explore potential serve predictive neurological disorders identify future directions optimizing protocols interpreting various contexts. By harnessing power may gain new insights health disease across lifespan, ultimately informing novel diagnostic therapeutic strategies. image

Language: Английский

Citations

8
Guggulsterone Selectively Modulates STAT-3, mTOR, and PPAR-Gamma Signaling in a Methylmercury-Exposed Experimental Neurotoxicity: Evidence from CSF, Blood Plasma, and Brain Samples DOI
Sumit Kumar, Sidharth Mehan, Zuber Khan

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(8), P. 5161 - 5193

Published: Jan. 3, 2024

Language: Английский

Citations

7
Nature inspired nanomaterials, advancements in green synthesis for biological sustainability DOI
Akhtar Rasool,

S Sri,

Muhammad Zulfajri

et al.

Inorganic Chemistry Communications, Journal Year: 2024, Volume and Issue: 169, P. 112954 - 112954

Published: Aug. 8, 2024

Language: Английский

Citations

7
Navigating the metabolic maze: anomalies in fatty acid and cholesterol processes in Alzheimer’s astrocytes DOI Creative Commons
Xiaoyu Zhang, Chuanying Chen, Yi Liu

et al.

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: March 23, 2024

Abstract Alzheimer’s disease (AD) is the most common cause of dementia, and its underlying mechanisms have been a subject great interest. The mainstream theory AD pathology suggests that primarily associated with tau protein amyloid-beta (Aβ). However, an increasing body research has revealed abnormalities in lipid metabolism may be important event throughout pathophysiology AD. Astrocytes, as members network brain, play significant role this event. study abnormal astrocytes provides new perspective for understanding pathogenesis This review focuses on fatty acids (FAs) cholesterol AD, discusses it from three perspectives: uptake, intracellular breakdown or synthesis metabolism, efflux transport. We found that, despite accumulation their own acids, cannot efficiently uptake neurons, leading to acid within neurons resulting lipotoxicity. In terms exhibit decrease endogenous due exogenous cholesterol. Through thorough investigation these metabolic abnormalities, we can provide insights future therapeutic strategies by literature navigate complex maze bring hope patients disease.

Language: Английский

Citations

6