scholarly journals The age-regulated zinc finger factor ZNF367 is a new modulator of embryonic neurogenesis

2018 ◽  
Author(s):  
Valentina Naef ◽  
Sara Monticelli ◽  
Debora Corsinovi ◽  
Maria Teresa Mazzetto ◽  
Alessandro Cellerino ◽  
...  
Keyword(s):  
Population Aging ◽  
Candidate Gene Approach ◽  
Loss Of Function ◽  
Neuronal Function ◽  
Embryonic Neurogenesis ◽  
Age Related ◽  
The Central Nervous System ◽  
Brain Age ◽  
Global Population

AbstractGlobal population aging is one of the major social and economic challenges of contemporary society. During aging the progressive decline in physiological functions has serious consequences for all organs including brain. The age-related incidence of neurodegenerative diseases coincides with the sharp decline of the amount and functionality of adult neural stem cells. Recently, we identified a short list of brain age-regulated genes by means of next-generation sequencing. Among them znf367 codes for a transcription factor that represents a central node in gene coregulation networks during aging but its function, in the central nervous system (CNS), is completely unknown. As proof of concept we analyzed the role of znf367 during neurogenesis. By means of a gene loss of function approach limited to the CNS, we suggested that znf367 might act as a key controller of the neuroblasts cell cycle, particularly in the progression of mitosis and spindle check-point. Using a candidate gene approach, based on a weighted-gene co-expression network analysis, we suggested possible targets of znf367 such as fancd2 and ska3. The age-related decline of znf367 well correlated with its role during embryonic neurogenesis opening new lines of investigation to improved maintenance and even repair of neuronal function.

scholarly journals The Role of the Innate Immune System in Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Eye on Microglia

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Elisa Ridolfi ◽  
Cinzia Barone ◽  
Elio Scarpini ◽  
Daniela Galimberti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Lobar Degeneration ◽  
Environmental Changes ◽  
Current Evidence ◽  
Neuronal Function ◽  
Immune Effector ◽  
Effector Cells ◽  
The Central Nervous System

In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

scholarly journals Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Colony Stimulating Factor ◽  
Loss Of Function ◽  
Axonal Spheroids ◽  
The Central Nervous System ◽  
Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

COGNITIVE AGING AND COGNITIVE RESERVE: POINT OF CONTACT

2020 ◽  
pp. 256-264
Author(s):  
В. С. Мякотных ◽  
А. П. Сиденкова ◽  
Е. С. Остапчук ◽  
И. А. Кулакова ◽  
Н. А. Белых ◽  
...  
Keyword(s):  
Cognitive Aging ◽  
Cognitive Reserve ◽  
Cognitive Disorders ◽  
The Elderly ◽  
Educational Process ◽  
Special Role ◽  
Age Related ◽  
The Central Nervous System ◽  
The One

Высокий риск когнитивных расстройств у лиц пожилого и старческого возраста заставляет, с одной стороны, искать их причины, с другой - возможности профилактики. В связи с этим в последние годы получило распространение понятие когнитивного резерва, подразумевающего совокупность количественных параметров головного мозга и его способности сохранять высокую функциональную активность в процессе старения и на фоне связанной с возрастом патологии головного мозга. Представленный в статье материал на основе обзора научной литературы освещает два основных момента, касающихся возможности сохранения когнитивного резерва, - гендерный и образовательный факторы. Указывается на разные возможности женщин и мужчин, связанные со структурными и функциональными особенностями ЦНС у представителей разного пола, и на особую роль поддерживаемого в течение всей жизни образовательного процесса. Обозначена авторская позиция о необходимости разделения понятий образования и образованности, то есть уровня общей культуры и создания удобного инструмента для определения последнего. Это, в свою очередь, помогло бы в разработке модели когнитивного резерва, нацеленной на предотвращение трансформации физиологического когнитивного старения в патологическое. The high risk of cognitive disorders in the elderly and senile age makes, on the one hand, to look for their causes, on the other - the possibility of prevention. In this regard, in recent years, the concept of cognitive reserve has become widespread, implying a set of quantitative parameters of the brain and its ability to maintain high functional activity in the process of aging and against the background of age-related brain pathology. The material presented in the article on the basis of the review of scientific literature highlights two main points concerning the possibility of preserving the cognitive reserve-gender and educational factors. It is pointed to the different opportunities of women and men associated with the structural and functional characteristics of the Central nervous system in representatives of different sexes and the special role of the educational process supported throughout life. The author’s position on the need to separate the concepts of education and the level of General culture, and the creation of a convenient tool for determining the latter is indicated. This, in turn, would help in the development of a cognitive reserve model aimed at preventing the transformation of physiological cognitive aging into pathological aging.

The role of Xenopus dickkopf1 in prechordal plate specification and neural patterning

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4981-4992 ◽  
Author(s):  
O. Kazanskaya ◽  
A. Glinka ◽  
C. Niehrs
Keyword(s):  
Target Genes ◽  
Loss Of Function ◽  
Dorsoventral Patterning ◽  
Gastrula Stage ◽  
Neural Patterning ◽  
Prechordal Plate ◽  
Wnt Inhibitor ◽  
The Central Nervous System ◽  
Wnt Inhibitors

Dickkopf1 (dkk1) encodes a secreted WNT inhibitor expressed in Spemann's organizer, which has been implicated in head induction in Xenopus. Here we have analyzed the role of dkk1 in endomesoderm specification and neural patterning by gain- and loss-of-function approaches. We find that dkk1, unlike other WNT inhibitors, is able to induce functional prechordal plate, which explains its ability to induce secondary heads with bilateral eyes. This may be due to differential WNT inhibition since dkk1, unlike frzb, inhibits Wnt3a signalling. Injection of inhibitory antiDkk1 antibodies reveals that dkk1 is not only sufficient but also required for prechordal plate formation but not for notochord formation. In the neural plate dkk1 is required for anteroposterior and dorsoventral patterning between mes- and telencephalon, where dkk1 promotes anterior and ventral fates. Both the requirement of anterior explants for dkk1 function and their ability to respond to dkk1 terminate at late gastrula stage. Xenopus embryos posteriorized with bFGF, BMP4 and Smads are rescued by dkk1. dkk1 does not interfere with the ability of bFGF to induce its immediate early target gene Xbra, indicating that its effect is indirect. In contrast, there is cross-talk between BMP and WNT signalling, since induction of BMP target genes is sensitive to WNT inhibitors until the early gastrula stage. Embryos treated with retinoic acid (RA) are not rescued by dkk1 and RA affects the central nervous system (CNS) more posterior than dkk1, suggesting that WNTs and retinoids may act to pattern anterior and posterior CNS, respectively, during gastrulation.

scholarly journals Loss of Wwox Causes Defective Development of Cerebral Cortex with Hypomyelination in a Rat Model of Lethal Dwarfism with Epilepsy

2019 ◽  
Vol 20 (14) ◽  
pp. 3596 ◽  
Author(s):  
Yuki Tochigi ◽  
Yutaka Takamatsu ◽  
Jun Nakane ◽  
Rika Nakai ◽  
Kentaro Katayama ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Rat Model ◽  
Physiological Role ◽  
Early Death ◽  
Neurite Growth ◽  
Loss Of Function ◽  
Age Related ◽  
Putative Tumor Suppressor ◽  
Severe Reduction

WW domain-containing oxidoreductase (Wwox) is a putative tumor suppressor. Several germline mutations of Wwox have been associated with infant neurological disorders characterized by epilepsy, growth retardation, and early death. Less is known, however, about the pathological link between Wwox mutations and these disorders or the physiological role of Wwox in brain development. In this study, we examined age-related expression and histological localization of Wwox in forebrains as well as the effects of loss of function mutations in the Wwox gene in the immature cortex of a rat model of lethal dwarfism with epilepsy (lde/lde). Immunostaining revealed that Wwox is expressed in neurons, astrocytes, and oligodendrocytes. lde/lde cortices were characterized by a reduction in neurite growth without a reduced number of neurons, severe reduction in myelination with a reduced number of mature oligodendrocytes, and a reduction in cell populations of astrocytes and microglia. These results indicate that Wwox is essential for normal development of neurons and glial cells in the cerebral cortex.

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

2015 ◽  
Vol 128 (12) ◽  
pp. 839-861 ◽  
Author(s):  
Dionne E.M. Maessen ◽  
Coen D.A. Stehouwer ◽  
Casper G. Schalkwijk
Keyword(s):  
Advanced Glycation Endproducts ◽  
Treatment Strategies ◽  
Glyoxalase System ◽  
Dicarbonyl Compound ◽  
Glycation Endproducts ◽  
Age Related ◽  
Key Enzyme ◽  
The Central Nervous System ◽  
New Treatment

The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

scholarly journals Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice

2011 ◽  
Vol 208 (9) ◽  
pp. 1835-1847 ◽  
Author(s):  
Gwénola Boulday ◽  
Noemi Rudini ◽  
Luigi Maddaluno ◽  
Anne Blécon ◽  
Minh Arnould ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Vascular Malformations ◽  
Vascular Lesions ◽  
Developmental Timing ◽  
Cerebral Cavernous Malformations ◽  
Loss Of Function ◽  
Cavernous Malformations ◽  
The Central Nervous System ◽  
Dominant Condition

Cerebral cavernous malformations (CCM) are vascular malformations of the central nervous system (CNS) that lead to cerebral hemorrhages. Familial CCM occurs as an autosomal dominant condition caused by loss-of-function mutations in one of the three CCM genes. Constitutive or tissue-specific ablation of any of the Ccm genes in mice previously established the crucial role of Ccm gene expression in endothelial cells for proper angiogenesis. However, embryonic lethality precluded the development of relevant CCM mouse models. Here, we show that endothelial-specific Ccm2 deletion at postnatal day 1 (P1) in mice results in vascular lesions mimicking human CCM lesions. Consistent with CCM1/3 involvement in the same human disease, deletion of Ccm1/3 at P1 in mice results in similar CCM lesions. The lesions are located in the cerebellum and the retina, two organs undergoing intense postnatal angiogenesis. Despite a pan-endothelial Ccm2 deletion, CCM lesions are restricted to the venous bed. Notably, the consequences of Ccm2 loss depend on the developmental timing of Ccm2 ablation. This work provides a highly penetrant and relevant CCM mouse model.

scholarly journals Astroglial Connexins in Neurodegenerative Diseases

2021 ◽  
Vol 14 ◽  
Author(s):  
Xiaomin Huang ◽  
Yixun Su ◽  
Nan Wang ◽  
Hui Li ◽  
Zhigang Li ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuronal Function ◽  
Gap Junction Channels ◽  
Normal Functions ◽  
Functional Remodeling ◽  
The Central Nervous System ◽  
Key Aspects ◽  
And Function ◽  
Lateral Sclerosis

Astrocytes play a crucial role in the maintenance of the normal functions of the Central Nervous System (CNS). During the pathogenesis of neurodegenerative diseases, astrocytes undergo morphological and functional remodeling, a process called reactive astrogliosis, in response to the insults to the CNS. One of the key aspects of the reactive astrocytes is the change in the expression and function of connexins. Connexins are channel proteins that highly expressed in astrocytes, forming gap junction channels and hemichannels, allowing diffusional trafficking of small molecules. Alterations of astrocytic connexin expression and function found in neurodegenerative diseases have been shown to affect the disease progression by changing neuronal function and survival. In this review, we will summarize the role of astroglial connexins in neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Also, we will discuss why targeting connexins can be a plausible therapeutic strategy to manage these neurodegenerative diseases.

scholarly journals Elastin-Derived Peptides in the Central Nervous System: Friend or Foe

2021 ◽  
Author(s):  
Konrad A. Szychowski ◽  
Bartosz Skóra ◽  
Anna K. Wójtowicz
Keyword(s):  
Nervous System ◽  
Matrix Proteins ◽  
Brain Vessels ◽  
Current State ◽  
Model Of Alzheimer’S Disease ◽  
Elastin Degradation ◽  
Age Related ◽  
The Central Nervous System ◽  
Structural Matrix

AbstractElastin is one of the main structural matrix proteins of the arteries, lung, cartilage, elastic ligaments, brain vessels, and skin. These elastin fibers display incredible resilience and structural stability with long half-life. However, during some physiological and pathophysiological conditions, elastin is prone to proteolytic degradation and, due to the extremely low turnover rate, its degradation is practically an irreversible and irreparable phenomenon. As a result of elastin degradation, new peptides called elastin-derived peptides (EDPs) are formed. A growing body of evidence suggests that these peptides play an important role in the development of age-related vascular disease. They are also detected in the cerebrospinal fluid of healthy people, and their amount increases in patients after ischemic stroke. Recently, elastin-like polypeptides have been reported to induce overproduction of beta-amyloid in a model of Alzheimer's disease. Nevertheless, the role and mechanism of action of EDPs in the nervous system is largely unknown and limited to only a few studies. The article summarizes the current state of knowledge on the role of EDPs in the nervous system.

scholarly journals Homocysteine and Age-Related Central Nervous System Diseases: Role of Inflammation

2021 ◽  
Vol 22 (12) ◽  
pp. 6259
Author(s):  
Amany Tawfik ◽  
Nehal M. Elsherbiny ◽  
Yusra Zaidi ◽  
Pragya Rajpurohit
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Barrier Function ◽  
Underlying Mechanism ◽  
Age Related Macular Degeneration ◽  
Barrier Dysfunction ◽  
Age Related ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Hyperhomocysteinemia (HHcy) is remarkably common among the aging population. The relation between HHcy and the development of neurodegenerative diseases, such as Alzheimer’s disease (AD) and eye diseases, and age-related macular degeneration (AMD) and diabetic retinopathy (DR) in elderly people, has been established. Disruption of the blood barrier function of the brain and retina is one of the most important underlying mechanisms associated with HHcy-induced neurodegenerative and retinal disorders. Impairment of the barrier function triggers inflammatory events that worsen disease pathology. Studies have shown that AD patients also suffer from visual impairments. As an extension of the central nervous system, the retina has been suggested as a prominent site of AD pathology. This review highlights inflammation as a possible underlying mechanism of HHcy-induced barrier dysfunction and neurovascular injury in aging diseases accompanied by HHcy, focusing on AD.

Sign in / Sign up

Export Citation Format

Share Document