Neuroscientist最新文献_第7页

The Endoplasmic Reticulum and Its Contacts: Emerging Roles in Axon Development, Neurotransmission, and Degeneration. 内质网及其联系：轴突发育、神经传递和退化中的新作用

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-10-01 Epub Date: 2023-03-24 DOI: 10.1177/10738584231162810

Marijn Kuijpers, Phuong T Nguyen, Volker Haucke

引用次数: 0

α-Synuclein: Multiple pathogenic roles in trafficking and proteostasis pathways in Parkinson's disease. α-突触核蛋白：在帕金森病的转运和蛋白稳态途径中的多重致病作用

IF 3.9 3区医学

Neuroscientist Pub Date : 2024-10-01 Epub Date: 2024-02-29 DOI: 10.1177/10738584241232963

Annie J Zalon, Drew J Quiriconi, Caleb Pitcairn, Joseph R Mazzulli

{"title":"α-Synuclein: Multiple pathogenic roles in trafficking and proteostasis pathways in Parkinson's disease.","authors":"Annie J Zalon, Drew J Quiriconi, Caleb Pitcairn, Joseph R Mazzulli","doi":"10.1177/10738584241232963","DOIUrl":"10.1177/10738584241232963","url":null,"abstract":"Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the midbrain. A hallmark of both familial and sporadic PD is the presence of Lewy body inclusions composed mainly of aggregated α-synuclein (α-syn), a presynaptic protein encoded by the SNCA gene. The mechanisms driving the relationship between α-syn accumulation and neurodegeneration are not completely understood, although recent evidence indicates that multiple branches of the proteostasis pathway are simultaneously perturbed when α-syn aberrantly accumulates within neurons. Studies from patient-derived midbrain cultures that develop α-syn pathology through the endogenous expression of PD-causing mutations show that proteostasis disruption occurs at the level of synthesis/folding in the endoplasmic reticulum (ER), downstream ER-Golgi trafficking, and autophagic-lysosomal clearance. Here, we review the fundamentals of protein transport, highlighting the specific steps where α-syn accumulation may intervene and the downstream effects on proteostasis. Current therapeutic efforts are focused on targeting single pathways or proteins, but the multifaceted pathogenic role of α-syn throughout the proteostasis pathway suggests that manipulating several targets simultaneously will provide more effective disease-modifying therapies for PD and other synucleinopathies.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"612-635"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration. 阿尔茨海默病的杜鹃花假说：功能性缺铁促进神经退行性变

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-10-01 Epub Date: 2023-08-20 DOI: 10.1177/10738584231191743

Steven M LeVine

{"title":"The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration.","authors":"Steven M LeVine","doi":"10.1177/10738584231191743","DOIUrl":"10.1177/10738584231191743","url":null,"abstract":"Chlorosis in azaleas is characterized by an interveinal yellowing of leaves that is typically caused by a deficiency of iron. This condition is usually due to the inability of cells to properly acquire iron as a consequence of unfavorable conditions, such as an elevated pH, rather than insufficient iron levels. The causes and effects of chlorosis were found to have similarities with those pertaining to a recently presented hypothesis that describes a pathogenic process in Alzheimer disease. This hypothesis states that iron becomes sequestered (e.g., by amyloid β and tau), causing a functional deficiency of iron that disrupts biochemical processes leading to neurodegeneration. Additional mechanisms that contribute to iron becoming unavailable include iron-containing structures not undergoing proper recycling (e.g., disrupted mitophagy and altered ferritinophagy) and failure to successfully translocate iron from one compartment to another (e.g., due to impaired lysosomal acidification). Other contributors to a functional deficiency of iron in patients with Alzheimer disease include altered metabolism of heme or altered production of iron-containing proteins and their partners (e.g., subunits, upstream proteins). A review of the evidence supporting this hypothesis is presented. Also, parallels between the mechanisms underlying a functional iron-deficient state in Alzheimer disease and those occurring for chlorosis in plants are discussed. Finally, a model describing the generation of a functional iron deficiency in Alzheimer disease is put forward.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"525-544"},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10876915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10210134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SARM1-Dependent Axon Degeneration: Nucleotide Signaling, Neurodegenerative Disorders, Toxicity, and Therapeutic Opportunities. SARM1 依赖性轴突退化：核苷酸信号、神经退行性疾病、毒性和治疗机会。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-08-01 Epub Date: 2023-03-31 DOI: 10.1177/10738584231162508

Helen Y McGuinness, Weixi Gu, Yun Shi, Bostjan Kobe, Thomas Ve

{"title":"SARM1-Dependent Axon Degeneration: Nucleotide Signaling, Neurodegenerative Disorders, Toxicity, and Therapeutic Opportunities.","authors":"Helen Y McGuinness, Weixi Gu, Yun Shi, Bostjan Kobe, Thomas Ve","doi":"10.1177/10738584231162508","DOIUrl":"10.1177/10738584231162508","url":null,"abstract":"Axons are an essential component of the nervous system, and axon degeneration is an early feature of many neurodegenerative disorders. The NAD+ metabolome plays an essential role in regulating axonal integrity. Axonal levels of NAD+ and its precursor NMN are controlled in large part by the NAD+ synthesizing survival factor NMNAT2 and the pro-neurodegenerative NADase SARM1, whose activation triggers axon destruction. SARM1 has emerged as a promising axon-specific target for therapeutic intervention, and its function, regulation, structure, and role in neurodegenerative diseases have been extensively characterized in recent years. In this review, we first introduce the key molecular players involved in the SARM1-dependent axon degeneration program. Next, we summarize recent major advances in our understanding of how SARM1 is kept inactive in healthy neurons and how it becomes activated in injured or diseased neurons, which has involved important insights from structural biology. Finally, we discuss the role of SARM1 in neurodegenerative disorders and environmental neurotoxicity and its potential as a therapeutic target.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"473-492"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9279120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tau, RNA, and RNA-Binding Proteins: Complex Interactions in Health and Neurodegenerative Diseases. Tau、RNA 和 RNA 结合蛋白：健康和神经退行性疾病中的复杂相互作用》。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-08-01 Epub Date: 2023-03-09 DOI: 10.1177/10738584231154551

Evan Lester, Roy Parker

引用次数: 0

COVID-19 and Long COVID: Disruption of the Neurovascular Unit, Blood-Brain Barrier, and Tight Junctions. COVID-19 和长 COVID：破坏神经血管单元、血脑屏障和紧密连接。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-08-01 Epub Date: 2023-09-11 DOI: 10.1177/10738584231194927

Duraisamy Kempuraj, Kristina K Aenlle, Jessica Cohen, Annette Mathew, Dylan Isler, Rajendra P Pangeni, Lubov Nathanson, Theoharis C Theoharides, Nancy G Klimas

{"title":"COVID-19 and Long COVID: Disruption of the Neurovascular Unit, Blood-Brain Barrier, and Tight Junctions.","authors":"Duraisamy Kempuraj, Kristina K Aenlle, Jessica Cohen, Annette Mathew, Dylan Isler, Rajendra P Pangeni, Lubov Nathanson, Theoharis C Theoharides, Nancy G Klimas","doi":"10.1177/10738584231194927","DOIUrl":"10.1177/10738584231194927","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), could affect brain structure and function. SARS-CoV-2 can enter the brain through different routes, including the olfactory, trigeminal, and vagus nerves, and through blood and immunocytes. SARS-CoV-2 may also enter the brain from the peripheral blood through a disrupted blood-brain barrier (BBB). The neurovascular unit in the brain, composed of neurons, astrocytes, endothelial cells, and pericytes, protects brain parenchyma by regulating the entry of substances from the blood. The endothelial cells, pericytes, and astrocytes highly express angiotensin converting enzyme 2 (ACE2), indicating that the BBB can be disturbed by SARS-CoV-2 and lead to derangements of tight junction and adherens junction proteins. This leads to increased BBB permeability, leakage of blood components, and movement of immune cells into the brain parenchyma. SARS-CoV-2 may also cross microvascular endothelial cells through an ACE2 receptor-associated pathway. The exact mechanism of BBB dysregulation in COVID-19/neuro-COVID is not clearly known, nor is the development of long COVID. Various blood biomarkers could indicate disease severity and neurologic complications in COVID-19 and help objectively diagnose those developing long COVID. This review highlights the importance of neurovascular and BBB disruption, as well as some potentially useful biomarkers in COVID-19, and long COVID/neuro-COVID.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"421-439"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10202301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Hypothalamic Perspective of Human Socioemotional Behavior. 人类社会情感行为的下丘脑视角。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-08-01 Epub Date: 2023-01-26 DOI: 10.1177/10738584221149647

Andrea Caria

{"title":"A Hypothalamic Perspective of Human Socioemotional Behavior.","authors":"Andrea Caria","doi":"10.1177/10738584221149647","DOIUrl":"10.1177/10738584221149647","url":null,"abstract":"Historical evidence from stimulation and lesion studies in animals and humans demonstrated a close association between the hypothalamus and typical and atypical socioemotional behavior. A central hypothalamic contribution to regulation of socioemotional responses was also provided indirectly by studies on oxytocin and arginine vasopressin. However, a limited number of studies have so far directly investigated the contribution of the hypothalamus in human socioemotional behavior. To reconsider the functional role of the evolutionarily conserved hypothalamic region in regulating human social behavior, here I provide a synthesis of neuroimaging investigations showing that the hypothalamus is involved in multiple and diverse facets of human socioemotional behavior through widespread functional interactions with other cortical and subcortical regions. These neuroimaging findings are then integrated with recent optogenetics studies in animals demonstrating that the hypothalamus plays a more active role in eliciting socioemotional responses and is not simply a downstream effector of higher-level brain systems. Building on the aforementioned evidence, the hypothalamus is argued to substantially contribute to a continuum of human socioemotional behaviors promoting survival and preservation of the species that extends from exploratory and approaching responses facilitating social bonding to aggressive and avoidance responses aimed to protect and defend formed relationships.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"399-420"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10628825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enteric Glia and Brain Astroglia: Complex Communication in Health and Disease along the Gut-Brain Axis. 肠胶质细胞和脑星状胶质细胞：肠胶质细胞和脑星状胶质细胞：沿着肠道-大脑轴在健康和疾病中的复杂交流》（Complex Communication in Health and Disease along the Gut-Brain Axis）。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-08-01 Epub Date: 2023-04-13 DOI: 10.1177/10738584231163460

Vanessa D'Antongiovanni, Carolina Pellegrini, Luca Antonioli, Chiara Ippolito, Cristina Segnani, Laura Benvenuti, Antonio D'Amati, Mariella Errede, Daniela Virgintino, Matteo Fornai, Nunzia Bernardini

{"title":"Enteric Glia and Brain Astroglia: Complex Communication in Health and Disease along the Gut-Brain Axis.","authors":"Vanessa D'Antongiovanni, Carolina Pellegrini, Luca Antonioli, Chiara Ippolito, Cristina Segnani, Laura Benvenuti, Antonio D'Amati, Mariella Errede, Daniela Virgintino, Matteo Fornai, Nunzia Bernardini","doi":"10.1177/10738584231163460","DOIUrl":"10.1177/10738584231163460","url":null,"abstract":"Several studies have provided interesting evidence about the role of the bidirectional communication between the gut and brain in the onset and development of several pathologic conditions, including inflammatory bowel diseases (IBDs), neurodegenerative diseases, and related comorbidities. Indeed, patients with IBD can experience neurologic disorders, including depression and cognitive impairment, besides typical intestinal symptoms. In parallel, patients with neurodegenerative disease, such as Parkinson disease and Alzheimer disease, are often characterized by the occurrence of functional gastrointestinal disorders. In this context, enteric glial cells and brain astrocytes are emerging as pivotal players in the initiation/maintenance of neuroinflammatory responses, which appear to contribute to the alterations of intestinal and neurologic functions observed in patients with IBD and neurodegenerative disorders. The present review was conceived to provide a comprehensive and critical overview of the available knowledge on the morphologic, molecular, and functional changes occurring in the enteric glia and brain astroglia in IBDs and neurologic disorders. In addition, our intent is to identify whether such alterations could represent a common denominator involved in the onset of comorbidities associated with the aforementioned disorders. This might help to identify putative targets useful to develop novel pharmacologic approaches for the therapeutic management of such disturbances.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":" ","pages":"493-510"},"PeriodicalIF":3.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9644612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondria in Aging and Alzheimer's Disease: Focus on Mitophagy. 衰老和阿尔茨海默病中的线粒体：关注线粒体吞噬。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-08-01 Epub Date: 2023-01-03 DOI: 10.1177/10738584221139761

Jangampalli Adi Pradeepkiran, Javaria Baig, Ashley Seman, P Hemachandra Reddy

引用次数: 0

Early-Onset Psychosis and Gray and White Matter Volume Abnormalities. 早发精神病与灰质和白质体积异常。

IF 3.5 3区医学

Neuroscientist Pub Date : 2024-08-01 DOI: 10.1177/10738584241260360a

引用次数: 0