Neuroscience Insights最新文献

The 3D Genome in Brain Development: An Exploration of Molecular Mechanisms and Experimental Methods. 大脑发育中的 3D 基因组：分子机理和实验方法的探索。

IF 2.9

Neuroscience Insights Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI: 10.1177/26331055241293455

Samir Rahman, Panos Roussos

{"title":"The 3D Genome in Brain Development: An Exploration of Molecular Mechanisms and Experimental Methods.","authors":"Samir Rahman, Panos Roussos","doi":"10.1177/26331055241293455","DOIUrl":"10.1177/26331055241293455","url":null,"abstract":"The human brain contains multiple cell types that are spatially organized into functionally distinct regions. The proper development of the brain requires complex gene regulation mechanisms in both neurons and the non-neuronal cell types that support neuronal function. Studies across the last decade have discovered that the 3D nuclear organization of the genome is instrumental in the regulation of gene expression in the diverse cell types of the brain. In this review, we describe the fundamental biochemical mechanisms that regulate the 3D genome, and comprehensively describe in vitro and ex vivo studies on mouse and human brain development that have characterized the roles of the 3D genome in gene regulation. We highlight the significance of the 3D genome in linking distal enhancers to their target promoters, which provides insights on the etiology of psychiatric and neurological disorders, as the genetic variants associated with these disorders are primarily located in noncoding regulatory regions. We also describe the molecular mechanisms that regulate chromatin folding and gene expression in neurons. Furthermore, we describe studies with an evolutionary perspective, which have investigated features that are conserved from mice to human, as well as human gained 3D chromatin features. Although most of the insights on disease and molecular mechanisms have been obtained from bulk 3C based experiments, we also highlight other approaches that have been developed recently, such as single cell 3C approaches, as well as non-3C based approaches. In our future perspectives, we highlight the gaps in our current knowledge and emphasize the need for 3D genome engineering and live cell imaging approaches to elucidate mechanisms and temporal dynamics of chromatin interactions, respectively.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ischemic Stroke: Pathophysiology and Evolving Treatment Approaches. 缺血性中风：病理生理学和不断发展的治疗方法。

IF 2.9

Neuroscience Insights Pub Date : 2024-10-22 eCollection Date: 2024-01-01 DOI: 10.1177/26331055241292600

Dhriti Majumder

引用次数: 0

Increased Resting-State BOLD Turnover (TBOLD) is Associated With Decreased Cognitive Performance During Aging. 静息态 BOLD 转化（TBOLD）的增加与衰老过程中认知能力的下降有关。

IF 2.9

Neuroscience Insights Pub Date : 2024-10-21 eCollection Date: 2024-01-01 DOI: 10.1177/26331055241292592

Lisa M James, Peka Christova, Apostolos P Georgopoulos

{"title":"Increased Resting-State BOLD Turnover (TBOLD) is Associated With Decreased Cognitive Performance During Aging.","authors":"Lisa M James, Peka Christova, Apostolos P Georgopoulos","doi":"10.1177/26331055241292592","DOIUrl":"https://doi.org/10.1177/26331055241292592","url":null,"abstract":"Increasing evidence documents turnover of the resting-state blood-oxygen-level dependent signal (TBOLD) as a key measure of local cortical brain status. Here we evaluated contemporaneous and lagged associations between TBOLD and cognitive function in 711 participants in the Human Connectome Project on Aging (HCP-A; 316 males and 395 females, age range 36-90 years). We found that TBOLD was negatively associated with Montreal Cognitive Assessment (MoCA) Total scores and with performance on 2 subscales, Delayed Recall and Visuospatial/Executive Function, controlling for sex, age, and handedness. This negative association was largely documented across brain areas and was significantly stronger in the left hemisphere compared to the right. In addition, analyses evaluating forward lagged crosscorrelations between TBOLD and cognitive performance demonstrated that TBOLD predicted decrements in future performance on MoCA Total score, Delayed Recall, and Visuospatial/Executive Function subscales, controlling for sex and handedness. Taken together, we found that increased TBOLD is associated with decreased cognitive performance contemporaneously and in the future. On the hypothesis that increased TBOLD is the outcome of neuroinflammatory processes, these findings provide a mechanism linking neuroinflammation with decreased cognitive performance.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cerebral Proteomic Changes in the rTg-D Rat Model of Cerebral Amyloid Angiopathy Type-2 With Cortical Microhemorrhages and Cognitive Impairments. 伴有皮质微出血和认知障碍的 2 型脑淀粉样血管病 rTg-D 大鼠模型的脑蛋白质组变化

IF 2.9

Neuroscience Insights Pub Date : 2024-10-08 eCollection Date: 2024-01-01 DOI: 10.1177/26331055241288172

Joseph M Schrader, Mark Majchrzak, Feng Xu, Hedok Lee, Kevin Agostinucci, Judianne Davis, Helene Benveniste, William E Van Nostrand

{"title":"Cerebral Proteomic Changes in the rTg-D Rat Model of Cerebral Amyloid Angiopathy Type-2 With Cortical Microhemorrhages and Cognitive Impairments.","authors":"Joseph M Schrader, Mark Majchrzak, Feng Xu, Hedok Lee, Kevin Agostinucci, Judianne Davis, Helene Benveniste, William E Van Nostrand","doi":"10.1177/26331055241288172","DOIUrl":"10.1177/26331055241288172","url":null,"abstract":"Cerebral amyloid angiopathy (CAA) is a common disorder of the elderly, a prominent comorbidity of Alzheimer's disease, and causes vascular cognitive impairment and dementia. Previously, we generated a novel transgenic rat model (rTg-D) that produces human familial CAA Dutch E22Q mutant amyloid β-protein (Aβ) in brain and develops arteriolar CAA type-2. Here, we show that deposition of fibrillar Aβ promotes arteriolar smooth muscle cell loss and cerebral microhemorrhages that can be detected by magnetic resonance imaging and confirmed by histopathology. Aged rTg-D rats also present with cognitive deficits. Cerebral proteomic analyses revealed 241 proteins that were significantly elevated with an increase of >50% in rTg-D rats presenting with CAA compared to wild-type rats. Fewer proteins were significantly decreased in rTg-D rats. Of note, high temperature requirement peptidase A (HTRA1), a proteinase linked to transforming growth factor beta 1 (TGF-β1) signaling, was elevated and found to accumulate in cerebral vessels harboring amyloid deposits. Pathway analysis indicated elevation of the TGF-β1 pathway and increased TGF-β1 levels were detected in rTg-D rats. In conclusion, the present findings provide new molecular insights into the pathogenesis of CAA and suggest a role for interactions between HTRA1 and TGF-β1 in the disease process.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent Updates on COVID-19 Associated Strokes. COVID-19 相关脑卒中的最新进展。

IF 2.9

Neuroscience Insights Pub Date : 2024-10-08 eCollection Date: 2024-01-01 DOI: 10.1177/26331055241287730

Colton Betts, Zane Ahlfinger, Mercy C Udeh, Batool F Kirmani

{"title":"Recent Updates on COVID-19 Associated Strokes.","authors":"Colton Betts, Zane Ahlfinger, Mercy C Udeh, Batool F Kirmani","doi":"10.1177/26331055241287730","DOIUrl":"10.1177/26331055241287730","url":null,"abstract":"The SARS-CoV-2 virus is primarily a respiratory virus, but, as it spread worldwide, it became apparent that there are multiple extrapulmonary manifestations. Reports arose of young and otherwise healthy patients presenting to emergency departments with large-vessel occlusions. Because of a rapidly evolving pandemic, conflicting data sometimes arose regarding the impact of the pandemic on strokes. COVID-19 can induce a hypercoagulable and a proinflammatory state through the interactions with the ACE-2 receptor. These mechanisms may lead to the strokes, both ischemic and hemorrhagic, that are seen in this infection. Strokes, in conjunction with COVID-19 infection, tended to be more disabling and portended a higher mortality. Treatment of these strokes was challenging, as emergency departments were strained with the high burden of COVID-19 admissions. Finally, vaccines against COVID-19 were widely administered, and their potential to cause stroke as an adverse event are discussed. This article will provide an in depth review of the recent updates about the incidence, epidemiology, pathophysiology, clinical presentation and treatment of strokes that are associated with COVID-19.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroimaging and the Investigation of Drug-Drug Interactions Involving Psychedelics. 神经影像学与涉及迷幻药的药物相互作用调查。

IF 2.9

Neuroscience Insights Pub Date : 2024-10-08 eCollection Date: 2024-01-01 DOI: 10.1177/26331055241286518

Matthew B Wall, Rebecca Harding, Natalie Ertl, Tommaso Barba, Rayyan Zafar, Mark Sweeney, David J Nutt, Eugenii A Rabiner, David Erritzoe

{"title":"Neuroimaging and the Investigation of Drug-Drug Interactions Involving Psychedelics.","authors":"Matthew B Wall, Rebecca Harding, Natalie Ertl, Tommaso Barba, Rayyan Zafar, Mark Sweeney, David J Nutt, Eugenii A Rabiner, David Erritzoe","doi":"10.1177/26331055241286518","DOIUrl":"10.1177/26331055241286518","url":null,"abstract":"Psychedelic therapies are an emerging class of treatments in psychiatry with great potential, however relatively little is known about their interactions with other commonly used psychiatric medications. As psychedelic therapies become more widespread and move closer to the clinic, they likely will need to be integrated into existing treatment models which may include one or more traditional pharmacological therapies, meaning an awareness of potential drug-drug interactions will become vital. This commentary outlines some of the issues surrounding the study of drug-drug interactions of this type, provides a summary of some of the relevant key results to date, and charts a way forward which relies crucially on multimodal neuroimaging investigations. Studies in humans which combine Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI), plus ancillary measures, are likely to provide the most comprehensive assessment of drug-drug interactions involving psychedelics and the relevant effects at multiple levels of the drug response (molecular, functional, and clinical).","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GABA, Aging and Exercise: Functional and Intervention Considerations. GABA、衰老和运动：功能和干预考虑因素。

IF 2.9

Neuroscience Insights Pub Date : 2024-09-26 eCollection Date: 2024-01-01 DOI: 10.1177/26331055241285880

Tom S Novak, Keith M McGregor, Lisa C Krishnamurthy, Alexandra Evancho, Kevin Mammino, Courtney E Walters, Ashton Weber, Joe R Nocera

{"title":"GABA, Aging and Exercise: Functional and Intervention Considerations.","authors":"Tom S Novak, Keith M McGregor, Lisa C Krishnamurthy, Alexandra Evancho, Kevin Mammino, Courtney E Walters, Ashton Weber, Joe R Nocera","doi":"10.1177/26331055241285880","DOIUrl":"10.1177/26331055241285880","url":null,"abstract":"The global growth of an aging population is expected to coincide with an increase in aging-related pathologies, including those related to brain health. Thus, the potential for accelerated cognitive health declines due to adverse aging is expected to have profound social and economic implications. However, the progression to pathological conditions is not an inevitable part of aging. In fact, engaging in activities that improve cardiovascular fitness appears to be a means that offers the benefits of maintaining and/or improving cognitive health in older age. However, to date, the underlying mechanisms responsible for improved central nervous system health and function with exercise are not yet fully elucidated. Consequently, there is considerable interest in studies aimed at understanding the neurophysiological benefits of exercise on aging. One such area of study suggests that the improvements in brain health via exercise are, in part, driven by the recovery of inhibitory processes related to the neurotransmitter gamma-aminobutyric acid (GABA). In the present review, we highlight the opposing effects of aging and exercise on cortical inhibition and the GABAergic system's functional integrity. We highlight these changes in GABA function by reviewing work with in vivo measurements: transcranial magnetic stimulation (TMS) and magnetic resonance spectroscopy (MRS). We also highlight recent and significant technological and methodological advances in assessing the GABAergic system's integrity with TMS and MRS. We then discuss potential future research directions to inform mechanistic GABA study targeted to improve health and function in aging. We conclude by highlighting the significance of understanding the effects of exercise and aging, its influence on GABA levels, and why a better understanding is crucial to allow for more targeted and effective interventions aimed to ultimately improve age-related decline in aging.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiple Sclerosis and COVID-19: An Overview on Risk, Severity, and Association With Disease Modifying Therapies. 多发性硬化症与 COVID-19：多发性硬化症与 COVID-19：风险、严重程度以及与疾病改变疗法的关联概述。

IF 2.9

Neuroscience Insights Pub Date : 2024-09-24 eCollection Date: 2024-01-01 DOI: 10.1177/26331055241265668

Mary Hollist, Abraham Hollist, Katherine Au, Colton Betts, Maha Kirmani, Maaida Kirmani, Benjamin Armour, Mercy C Udeh, Batool F Kirmani

{"title":"Multiple Sclerosis and COVID-19: An Overview on Risk, Severity, and Association With Disease Modifying Therapies.","authors":"Mary Hollist, Abraham Hollist, Katherine Au, Colton Betts, Maha Kirmani, Maaida Kirmani, Benjamin Armour, Mercy C Udeh, Batool F Kirmani","doi":"10.1177/26331055241265668","DOIUrl":"https://doi.org/10.1177/26331055241265668","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, emerged in December 2019, sparking a global health crisis. While initially recognized as a respiratory illness, it has become evident that Coronavirus disease 2019 (COVID-19) also affects the central nervous system. This comprehensive review focuses on the neurological manifestations of COVID-19 and its impact on patients with preexisting neurological disorders, particularly those with multiple sclerosis (MS) receiving disease-modifying therapies. Advancements in management, including vaccinations, antiviral therapy, and targeted prophylaxis, have led to a decline in the incidence and severity of COVID-19. Nevertheless, significant complications persist, particularly in patients with advanced MS, who are highly vulnerable to infectious agents like SARS-CoV-2. This review explores the evolving understanding of MS and its association with SARS-CoV-2, encompassing neuroinvasiveness, pathogenesis, disease severity, and outcomes. Research findings reveal substantial neurological implications for some MS patients with COVID-19, with a potential risk of disease relapse and severity. A notable proportion of MS patients experiencing COVID-19 may manifest new symptoms, experience exacerbation of existing symptoms, or encounter both simultaneously, underscoring the diverse neurological effects of the virus. While vaccination and therapeutics have mitigated the overall impact, specific subgroups, especially those on anti-CD20 therapy and with existing disability, remain at higher risk, necessitating ongoing vigilance and tailored care.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142355759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cacao Ameliorates Amyloid Beta-Induced Cognitive and Non-Cognitive Disturbances. 可可能改善淀粉样β蛋白诱发的认知和非认知紊乱

IF 2.9

Neuroscience Insights Pub Date : 2024-09-17 eCollection Date: 2024-01-01 DOI: 10.1177/26331055241280638

Hamid Shokati Basir, Naser Mirazi, Alireza Komaki, Mahdi Ramezani, Abdolkarim Hosseini

{"title":"Cacao Ameliorates Amyloid Beta-Induced Cognitive and Non-Cognitive Disturbances.","authors":"Hamid Shokati Basir, Naser Mirazi, Alireza Komaki, Mahdi Ramezani, Abdolkarim Hosseini","doi":"10.1177/26331055241280638","DOIUrl":"10.1177/26331055241280638","url":null,"abstract":"Background: Alzheimer's disease (AD) is a progressive neurological disorder characterized by a wide range of cognitive and non-cognitive impairments. The present study was designed to investigate the potential effects of cacao on cognitive and non-cognitive performance and to identify the role of oxidative stress in an AD animal model induced by unilateral intracerebroventricular (U-ICV) injection of amyloid beta1-42 (Aβ1-42).Methods: Oral administration of cacao (0.5 g/kg/day) was performed for 60 consecutive days. Following 60 days, the open-field (OF) test, elevated plus-maze (EPM) test, novel object recognition (NOR) test, Barnes maze (BM) test, and Morris water maze (MWM) test were used to evaluate locomotor activity, anxiety-like behavior, recognition memory, and spatial memory, respectively. Total oxidant status (TOS) and total antioxidant capacity (TAC) in plasma were also examined. Furthermore, the number of healthy cells in the hippocampus's dentate gyrus (DG), CA1, and CA3 regions were identified using hematoxylin and eosin staining.Results: The results indicated that the injection of Aβ1-42 in rats led to recognition memory and spatial memory impairments, as well as increased anxiety. This was accompanied by decreased total antioxidant capacity (TAC), increased total oxidative stress (TOS), and increased neuronal death. Conversely, cacao treatment in AD rats improved memory function, reduced anxiety, modulated oxidative stress balance, and decreased neuronal death.Conclusion: The findings suggest that cacao's ability to improve the balance between oxidants and antioxidants and prevent neuronal loss may be the mechanism underlying its beneficial effect against AD-related cognitive and non-cognitive impairments.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val. CRISPR/CasRx 介导的 Rab7B 基因敲除可恢复佩里泽斯-默茨巴赫氏病相关 PLP1 p.Ala243Val 诱导的不完整细胞形状。

IF 2.9

Neuroscience Insights Pub Date : 2024-09-13 eCollection Date: 2024-01-01 DOI: 10.1177/26331055241276873

Nana Fukushima, Yuki Miyamoto, Junji Yamauchi

{"title":"CRISPR/CasRx-Mediated Knockdown of Rab7B Restores Incomplete Cell Shape Induced by Pelizaeus-Merzbacher Disease-Associated PLP1 p.Ala243Val.","authors":"Nana Fukushima, Yuki Miyamoto, Junji Yamauchi","doi":"10.1177/26331055241276873","DOIUrl":"https://doi.org/10.1177/26331055241276873","url":null,"abstract":"Pelizaeus-Merzbacher disease (PMD, currently known as hypomyelinating leukodystrophy type 1 [HLD1]) is a hereditary hypomyelinating and/or demyelinating disease associated with the proteolipid protein 1 (plp1) gene in the central nervous system (CNS). One of the major causes of this condition is incomplete or defective oligodendroglial cell myelin sheath formation triggered by endoplasmic reticulum (ER) stress and subsequent unfolded protein response (UPR). The HLD1-associated Ala-243-to-Val mutation (p.Ala243Val) of PLP1 is widely recognized to trigger defective oligodendroglial cell morphological differentiation, primarily due to ER stress. We have previously reported that knockdown of Rab7B (also known as Rab42), a small GTP/GDP-binding protein involved in intracellular vesicle trafficking around the lysosome, can recover chemical ER stress-induced incomplete cell shapes in the FBD-102b cell line, a model of oligodendroglial cell morphological differentiation. Here, we present findings indicating that incomplete cell shapes induced by PLP1 p.Ala243Val can be restored by knockdown of Rab7B using the clustered regularly interspaced short palindromic repeats (CRISPR) and CasRx (also known as Cas13d) system. Also, the knockdown promoted the trafficking of PLP1 p.Ala243Val to lysosome-associated membrane protein 1 (LAMP1)-positive organelles. These results highlight the unique role of Rab7B knockdown in modulating oligodendroglial cell morphological changes and potentially facilitating the transport of mutated PLP1 to LAMP1-positive organelles, suggesting its potential as a therapeutic target for alleviating HLD1 phenotypes, at least in part, at the molecular and cellular levels.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0