Translational Neurodegeneration最新文献

{"title":"A phase 1b randomized clinical trial of CT1812 to measure Aβ oligomer displacement in Alzheimer's disease using an indwelling CSF catheter.","authors":"Kelsie M LaBarbera, Yvette I Sheline, Nicholas J Izzo, Carla M Yuede, Lora Waybright, Raymond Yurko, Hannah M Edwards, Woodrow D Gardiner, Kaj Blennow, Henrik Zetterberg, Anne Börjesson-Hanson, Roger Morgan, Charles S Davis, Robert J Guttendorf, Lon S Schneider, Steven DeKosky, Harry LeVine, Michael Grundman, Anthony O Caggiano, John R Cirrito, Susan M Catalano, Mary E Hamby","doi":"10.1186/s40035-023-00358-w","DOIUrl":"10.1186/s40035-023-00358-w","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"12 1","pages":"24"},"PeriodicalIF":12.6,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9616499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life adversity as a risk factor for cognitive impairment and Alzheimer's disease.","authors":"Zhihai Huang, J Dedrick Jordan, Quanguang Zhang","doi":"10.1186/s40035-023-00355-z","DOIUrl":"10.1186/s40035-023-00355-z","url":null,"abstract":"<p><p>Neurological conditions, including cognitive impairment and Alzheimer's disease (AD), impose a huge burden on society, affecting millions of people globally. In addition to genetic factors, recent studies indicate that environmental and experiential factors may contribute to the pathogenesis of these diseases. Early life adversity (ELA) has a profound impact on brain function and health later in life. In rodent models, exposure to ELA results in specific cognitive deficits and aggravated AD pathology. Extensive concerns have been raised regarding the higher risk of developing cognitive impairments in people with a history of ELA. In this review, we scrutinize findings from human and animal studies focusing on the connection of ELA with cognitive impairment and AD. These discoveries suggest that ELA, especially at early postnatal stages, increases susceptibility to cognitive impairment and AD later in life. In terms of mechanisms, ELA could lead to dysregulation of the hypothalamus-pituitary-adrenal axis, altered gut microbiome, persistent inflammation, oligodendrocyte dysfunction, hypomyelination, and aberrant adult hippocampal neurogenesis. Crosstalks among these events may synergistically contribute to cognitive impairment later in life. Additionally, we discuss several interventions that may alleviate adverse consequences of ELA. Further investigation into this crucial area will help improve ELA management and reduce the burden of related neurological conditions.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"12 1","pages":"25"},"PeriodicalIF":12.6,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9544463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Links between COVID-19 and Parkinson's disease/Alzheimer's disease: reciprocal impacts, medical care strategies and underlying mechanisms.","authors":"Pei Huang,&nbsp;Lin-Yuan Zhang,&nbsp;Yu-Yan Tan,&nbsp;Sheng-Di Chen","doi":"10.1186/s40035-023-00349-x","DOIUrl":"https://doi.org/10.1186/s40035-023-00349-x","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"12 1","pages":"23"},"PeriodicalIF":12.6,"publicationDate":"2023-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9829209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Starburst amacrine cells, involved in visual motion perception, lose their synaptic input from dopaminergic amacrine cells and degenerate in Parkinson's disease patients.","authors":"Xavier Sánchez-Sáez,&nbsp;Isabel Ortuño-Lizarán,&nbsp;Carla Sánchez-Castillo,&nbsp;Pedro Lax,&nbsp;Nicolás Cuenca","doi":"10.1186/s40035-023-00360-2","DOIUrl":"https://doi.org/10.1186/s40035-023-00360-2","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"12 1","pages":"22"},"PeriodicalIF":12.6,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9456148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia.","authors":"Nuole Zhu,&nbsp;Miguel Santos-Santos,&nbsp;Ignacio Illán-Gala,&nbsp;Victor Montal,&nbsp;Teresa Estellés,&nbsp;Isabel Barroeta,&nbsp;Miren Altuna,&nbsp;Javier Arranz,&nbsp;Laia Muñoz,&nbsp;Olivia Belbin,&nbsp;Isabel Sala,&nbsp;Maria Belén Sánchez-Saudinós,&nbsp;Andrea Subirana,&nbsp;Laura Videla,&nbsp;Jordi Pegueroles,&nbsp;Rafael Blesa,&nbsp;Jordi Clarimón,&nbsp;Maria Carmona-Iragui,&nbsp;Juan Fortea,&nbsp;Alberto Lleó,&nbsp;Daniel Alcolea","doi":"10.1186/s40035-023-00351-3","DOIUrl":"https://doi.org/10.1186/s40035-023-00351-3","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"12 1","pages":"21"},"PeriodicalIF":12.6,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10169348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9505123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microtubule acetylation dyshomeostasis in Parkinson's disease.","authors":"Padmashri Naren,&nbsp;Khan Sabiya Samim,&nbsp;Kamatham Pushpa Tryphena,&nbsp;Lalitkumar K Vora,&nbsp;Saurabh Srivastava,&nbsp;Shashi Bala Singh,&nbsp;Dharmendra Kumar Khatri","doi":"10.1186/s40035-023-00354-0","DOIUrl":"https://doi.org/10.1186/s40035-023-00354-0","url":null,"abstract":"<p><p>The inter-neuronal communication occurring in extensively branched neuronal cells is achieved primarily through the microtubule (MT)-mediated axonal transport system. This mechanistically regulated system delivers cargos (proteins, mRNAs and organelles such as mitochondria) back and forth from the soma to the synapse. Motor proteins like kinesins and dynein mechanistically regulate polarized anterograde (from the soma to the synapse) and retrograde (from the synapse to the soma) commute of the cargos, respectively. Proficient axonal transport of such cargos is achieved by altering the microtubule stability via post-translational modifications (PTMs) of α- and β-tubulin heterodimers, core components constructing the MTs. Occurring within the lumen of MTs, K40 acetylation of α-tubulin via α-tubulin acetyl transferase and its subsequent deacetylation by HDAC6 and SIRT2 are widely scrutinized PTMs that make the MTs highly flexible, which in turn promotes their lifespan. The movement of various motor proteins, including kinesin-1 (responsible for axonal mitochondrial commute), is enhanced by this PTM, and dyshomeostasis of neuronal MT acetylation has been observed in a variety of neurodegenerative conditions, including Alzheimer's disease and Parkinson's disease (PD). PD is the second most common neurodegenerative condition and is closely associated with impaired MT dynamics and deregulated tubulin acetylation levels. Although the relationship between status of MT acetylation and progression of PD pathogenesis has become a chicken-and-egg question, our review aims to provide insights into the MT-mediated axonal commute of mitochondria and dyshomeostasis of MT acetylation in PD. The enzymatic regulators of MT acetylation along with their synthetic modulators have also been briefly explored. Moving towards a tubulin-based therapy that enhances MT acetylation could serve as a disease-modifying treatment in neurological conditions that lack it.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"12 1","pages":"20"},"PeriodicalIF":12.6,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9492355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An AARS1 variant identified to cause adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia.","authors":"Jingying Wu,&nbsp;Taotao Liu,&nbsp;Benyan Zhang,&nbsp;Chang Liu,&nbsp;Xinghua Luan,&nbsp;Li Cao","doi":"10.1186/s40035-023-00353-1","DOIUrl":"https://doi.org/10.1186/s40035-023-00353-1","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"12 1","pages":"19"},"PeriodicalIF":12.6,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9492349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases.","authors":"Sina Shadfar,&nbsp;Sonam Parakh,&nbsp;Md Shafi Jamali,&nbsp;Julie D Atkin","doi":"10.1186/s40035-023-00350-4","DOIUrl":"https://doi.org/10.1186/s40035-023-00350-4","url":null,"abstract":"<p><p>Redox homeostasis refers to the balance between the production of reactive oxygen species (ROS) as well as reactive nitrogen species (RNS), and their elimination by antioxidants. It is linked to all important cellular activities and oxidative stress is a result of imbalance between pro-oxidants and antioxidant species. Oxidative stress perturbs many cellular activities, including processes that maintain the integrity of DNA. Nucleic acids are highly reactive and therefore particularly susceptible to damage. The DNA damage response detects and repairs these DNA lesions. Efficient DNA repair processes are therefore essential for maintaining cellular viability, but they decline considerably during aging. DNA damage and deficiencies in DNA repair are increasingly described in age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease. Furthermore, oxidative stress has long been associated with these conditions. Moreover, both redox dysregulation and DNA damage increase significantly during aging, which is the biggest risk factor for neurodegenerative diseases. However, the links between redox dysfunction and DNA damage, and their joint contributions to pathophysiology in these conditions, are only just emerging. This review will discuss these associations and address the increasing evidence for redox dysregulation as an important and major source of DNA damage in neurodegenerative disorders. Understanding these connections may facilitate a better understanding of disease mechanisms, and ultimately lead to the design of better therapeutic strategies based on preventing both redox dysregulation and DNA damage.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"12 1","pages":"18"},"PeriodicalIF":12.6,"publicationDate":"2023-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9844908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Starburst amacrine cells, involved in visual motion perception, loose their synaptic input from dopaminergic amacrine cells and degenerate in Parkinson's disease patients.","authors":"Xavier Sánchez-Sáez,&nbsp;Isabel Ortuño-Lizarán,&nbsp;Carla Sánchez-Castillo,&nbsp;Pedro Lax,&nbsp;Nicolás Cuenca","doi":"10.1186/s40035-023-00348-y","DOIUrl":"https://doi.org/10.1186/s40035-023-00348-y","url":null,"abstract":"<p><strong>Background: </strong>The main clinical symptoms characteristic of Parkinson's disease (PD) are bradykinesia, tremor, and other motor deficits. However, non-motor symptoms, such as visual disturbances, can be identified at early stages of the disease. One of these symptoms is the impairment of visual motion perception. Hence, we sought to determine if the starburst amacrine cells, which are the main cellular type involved in motion direction selectivity, are degenerated in PD and if the dopaminergic system is related to this degeneration.</p><p><strong>Methods: </strong>Human eyes from control (n = 10) and PD (n = 9) donors were available for this study. Using immunohistochemistry and confocal microscopy, we quantified starburst amacrine cell density (choline acetyltransferase [ChAT]-positive cells) and the relationship between these cells and dopaminergic amacrine cells (tyrosine hydroxylase-positive cells and vesicular monoamine transporter-2-positive presynapses) in cross-sections and wholemount retinas.</p><p><strong>Results: </strong>First, we found two different ChAT amacrine populations in the human retina that presented different ChAT immunoreactivity intensity and different expression of calcium-binding proteins. Both populations are affected in PD and their density is reduced compared to controls. Also, we report, for the first time, synaptic contacts between dopaminergic amacrine cells and ChAT-positive cells in the human retina. We found that, in PD retinas, there is a reduction of the dopaminergic synaptic contacts into ChAT cells.</p><p><strong>Conclusions: </strong>Taken together, this work indicates degeneration of starburst amacrine cells in PD related to dopaminergic degeneration and that dopaminergic amacrine cells could modulate the function of starburst amacrine cells. Since motion perception circuitries are affected in PD, their assessment using visual tests could provide new insights into the diagnosis of PD.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"12 1","pages":"17"},"PeriodicalIF":12.6,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10071607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9436460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Argyrophilic grain disease is common in older adults and may be a risk factor for suicide: a study of Japanese forensic autopsy cases.","authors":"Koji Yoshida,&nbsp;Yukiko Hata,&nbsp;Shojiro Ichimata,&nbsp;Keitaro Okada,&nbsp;Naoki Nishida","doi":"10.1186/s40035-023-00352-2","DOIUrl":"https://doi.org/10.1186/s40035-023-00352-2","url":null,"abstract":"<p><strong>Background: </strong>Neuropathological diagnosis of argyrophilic grain disease (AGD) is currently based primarily on the combination of argyrophilic grain (AG) visualized using Gallyas-Braak silver staining, phosphorylated tau-positive pretangles, coiled bodies, and ballooned neuron detection. Although AGD is common in patients with dementia and/or prominent psychiatric symptoms, whether it is a distinct neurological disease entity or a by-product of the aging process remains unclear.</p><p><strong>Methods: </strong>In 1449 serial forensic autopsy cases > 40 years old (823 males and 525 females, aged 40-101 years, mean age 70.0 ± 14.1 years), we examined the frequency and comorbid pathology of AGD cases and investigated the clinical appearance by comparing those with non-AGD cases using the propensity score.</p><p><strong>Results: </strong>Of the 1449 cases, we detected 342 AGD cases (23.6%; mean age 79.7 years; 177 males and 165 females). The AGD frequency and stage increased with age (P < 0.001). Among AGD cases, 80 (23.4%) patients had dementia, and 51 (15.2%) had a history of psychiatric hospital visits. The frequency of suicide and history of psychiatric disorders were significantly higher in AGD cases than in AGD-negative cases, matched for age, sex, and comorbidity pathology, with a relative risk of suicide of 1.72 (1.30-2.26). The frequency of suicide was significantly higher in AGD cases than in non-AGD cases in female but not male cases. The relative risk of suicide increased to 2.27 (1.20-4.30) and 6.50 (1.58-26.76) in AGD patients with Lewy and progressive supranuclear palsy pathology, respectively, and decreased to 0.88 (0.38-2.10) in those with advanced AD pathology. In AGD cases, 23.4% had dementia; however, the difference was not significant after controlling for age, sex, and comorbid pathology.</p><p><strong>Conclusion: </strong>Our study demonstrated that AGD is a significant and isolated risk factor for psychiatric hospital visits and suicide completion. In older adults, AGs may contribute to the progression of functional impairment of the limbic system, which leads to psychiatric disorders and suicide attempts.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"12 1","pages":"16"},"PeriodicalIF":12.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9621451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}