共查询到20条相似文献,搜索用时 15 毫秒
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Bogomazova A. N. Eremeev A. V. Pozmogova G. E. Lagarkova M. A. 《Molecular Biology》2019,53(6):838-849
Molecular Biology - Polyglutamine diseases are rare, inherited neurodegenerative pathologies that arise as a result of expansion of trinucleotide CAG repeats in the coding segment of certain genes.... 相似文献
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Alzheimer’s disease (AD) is the most common type of neurodegenerative dementia that affects the elderly population. Nerve growth factor (NGF) contributes to the survival, regeneration and death of neurons during aging and in neurodegenerative diseases. Recently, research has shown that NGF is related to the pathology, mechanisms and symptoms of AD. Therefore, there is a need to summarize the new advancements in NGF research and its potential therapeutic implications in AD. In this review, we will focus on NGF distribution, production, and function; the interaction of Aβ and NGF; and the effect of different therapy methods on AD. In summary, we hope to describe the experimental and clinical data demonstrating the important roles of NGF for AD treatment. 相似文献
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Zhiyou Cai Nannuan Liu Chuanling Wang Biyong Qin Yingjun Zhou Ming Xiao Liying Chang Liang-Jun Yan Bin Zhao 《Cellular and molecular neurobiology》2016,36(4):483-495
Receptor for advanced glycation end products (RAGE) is a receptor of the immunoglobulin super family that plays various important roles under physiological and pathological conditions. Compelling evidence suggests that RAGE acts as both an inflammatory intermediary and a critical inducer of oxidative stress, underlying RAGE-induced Alzheimer-like pathophysiological changes that drive the process of Alzheimer’s disease (AD). A critical role of RAGE in AD includes beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangles, failure of synaptic transmission, and neuronal degeneration. The steady-state level of Aβ depends on the balance between production and clearance. RAGE plays an important role in the Aβ clearance. RAGE acts as an important transporter via regulating influx of circulating Aβ into brain, whereas the efflux of brain-derived Aβ into the circulation via BBB is implemented by LRP1. RAGE could be an important contributor to Aβ generation via enhancing the activity of β- and/or γ-secretases and activating inflammatory response and oxidative stress. However, sRAGE–Aβ interactions could inhibit Aβ neurotoxicity and promote Aβ clearance from brain. Meanwhile, RAGE could be a promoting factor for the synaptic dysfunction and neuronal circuit dysfunction which are both the material structure of cognition, and the physiological and pathological basis of cognition. In addition, RAGE could be a trigger for the pathogenesis of Aβ and tau hyper-phosphorylation which both participate in the process of cognitive impairment. Preclinical and clinical studies have supported that RAGE inhibitors could be useful in the treatment of AD. Thus, an effective measure to inhibit RAGE may be a novel drug target in AD. 相似文献
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Bezprozvanny I 《Neurochemical research》2011,36(7):1186-1197
Huntington’s disease (HD) and spinocerebellar ataxias (SCAs) are autosomal-dominant neurodegenerative disorders. HD is caused
by polyglutamine (polyQ) expansion in the amino-terminal region of a protein huntingtin (Htt) and primarily affects medium
spiny striatal neurons (MSN). Many SCAs are caused by polyQ-expansion in ataxin proteins and primarily affect cerebellar Purkinje
cells. The reasons for neuronal dysfunction and death in HD and SCAs remain poorly understood and no cure is available for
the patients. Our laboratory discovered that mutant huntingtin, ataxin-2 and ataxin-3 proteins specifically bind to the carboxy-terminal
region of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1), an intracellular Ca2+ release channel. Moreover, we found that association of mutant huntingtin or ataxins with IP3R1 causes sensitization of IP3R1 to activation by IP3 in planar lipid bilayers and in neuronal cells. These results suggested that deranged neuronal Ca2+ signaling might play an important role in pathogenesis of HD, SCA2 and SCA3. In support of this idea, we demonstrated a connection
between abnormal Ca2+ signaling and neuronal cell death in experiments with HD, SCA2 and SCA3 transgenic mouse models. Additional data in the literature
indicate that abnormal neuronal Ca2+ signaling may also play an important role in pathogenesis of SCAl, SCA5, SCA6, SCA14 and SCA15/16. Based on these results
I propose that IP3R and other Ca2+ signaling proteins should be considered as potential therapeutic targets for treatment of HD and SCAs. 相似文献
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Xiao-Guang Luo Ji-Juan Zhang Chao-Dong Zhang Rong Liu Lan Zheng Xi-Jin Wang Sheng-Di Chen Jian-Qing Ding 《Neurochemical research》2010,35(4):540-547
Microglia are the representative myeloid cells in the brain, and their over-activation plays an important role in the pathogenesis
of Parkinson’s disease (PD). Microglia activation is believed to be regulated by the CD200-CD200R signaling. As the peripheral
counterpart of microglia, monocyte-derived macrophages (MDMs) share the same progenitor and antigen markers, and they have
similar biological behaviors and mirror microglial function in the brain. Here, we studied CD200R expression and its regulation
in MDMs from 32 PD cases, 27 age-matched old controls, and 28 young controls. We found that the basal CD200R expression is
similar in MDMs from young control, old control and PD patients. However, the induction of CD200R expression in MDMs under
various conditions is impaired in the old groups, especially in PD patients. There was a selective decrease in CD200R expression
induced by co-culture with dying PC12 cells in MDMs from PD cases, as compared with MDMs from the age-matched controls. We
also found that the inducible CD200R expression correlated inversely with the onset age of PD and to tumor necrosis factor-α
(TNF-α) released from MDMs. These results suggest an intrinsic abnormality in the CD200-CD200R signaling in MDMs during aging
and, especially, in PD. We speculate that in the PD brain, microglia might undergo abnormalities similar to MDMs. 相似文献
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Federica Solca Barbara Poletti Stefano Zago Chiara Crespi Francesca Sassone Annalisa Lafronza Anna Maria Maraschi Jenny Sassone Vincenzo Silani Andrea Ciammola 《PloS one》2015,10(6)
Background and Objective
Counterfactual thinking (CFT) refers to the generation of mental simulations of alternatives to past events, actions and outcomes. CFT is a pervasive cognitive feature in every-day life and is closely related to decision-making, planning and problem-solving – all of which are cognitive processes linked to unimpaired frontal lobe functioning. Huntington’s Disease (HD) is a neurodegenerative disorder characterised by motor, behavioral and cognitive dysfunctions. Because an impairment in frontal and executive functions has been described in HD, we hypothesised that HD patients may have a CFT impairment.Methods
Tests of spontaneous counterfactual thoughts and counterfactual-derived inferences were administered to 24 symptomatic HD patients and 24 age- and sex-matched healthy subjects.Results
Our results show a significant impairment in the spontaneous generation of CFT and low performance on the Counterfactual Inference Test (CIT) in HD patients. Low performance on the spontaneous CFT test significantly correlates with impaired attention abilities, verbal fluency and frontal lobe efficiency, as measured by Trail Making Test – Part A, Phonemic Verbal Fluency Test and FAB.Conclusions
Spontaneous CFT and the use of this type of reasoning are impaired in HD patients. This deficit may be related to frontal lobe dysfunction, which is a hallmark of HD. Because CFT has a pervasive role in patients’ daily lives regarding their planning, decision making and problem solving skills, cognitive rehabilitation may improve HD patients’ ability to analyse current behaviors and future actions. 相似文献13.
The human genome is under continuous attack by a plethora of harmful agents. Without the development of several dedicated DNA repair pathways, the genome would have been destroyed and cell death, inevitable. However, while DNA repair enzymes generally maintain the integrity of the whole genome by properly repairing mutagenic and cytotoxic intermediates, there are cases in which the DNA repair machinery is implicated in causing disease rather than protecting against it. One case is the instability of gene-specific trinucleotides, the causative mutations of numerous disorders including Huntington’s disease. The DNA repair proteins induce mutations that are different from the genome-wide mutations that arise in the absence of repair enzymes; they occur at definite loci, they occur in specific tissues during development, and they are age-dependent. These latter characteristics make pluripotent stem cells a suitable model system for triplet repeat expansion disorders. Pluripotent stem cells can be kept in culture for a prolonged period of time and can easily be differentiated into any tissue, e.g., cells along the neural lineage. Here, we review the role of DNA repair proteins in the process of triplet repeat instability in Huntington’s disease and also the potential use of pluripotent stem cells to investigate neurodegenerative disorders. 相似文献
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Sukhorukov V. S. Voronkova A. S. Litvinova N. A. Baranich T. I. Illarioshkin S. N. 《Russian Journal of Genetics》2020,56(4):402-409
Russian Journal of Genetics - The present article reviews the rapidly growing body of research on the role of mitochondrial DNA (mtDNA) in the realization of individual risk of Parkinson’s... 相似文献
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Fotoohi Ahmad Moloudi Mohammad Raman Hosseini Saed Hassanzadeh Kambiz Feligioni Marco Izadpanah Esmael 《Neurochemical research》2021,46(6):1372-1379
Neurochemical Research - Huntington’s disease (HD) is a progressive, neurodegenerative and inherited disease and recent years have witnessed the understanding of the cellular and molecular... 相似文献
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Rajasree Nambron Edina Silajd?i? Eirini Kalliolia Chris Ottolenghi Peter Hindmarsh Nathan R. Hill Seán J. Costelloe Nicholas G. Martin Vincenzo Positano Hilary C. Watt Chris Frost Maria Bj?rkqvist Thomas T. Warner 《PloS one》2016,11(1)
Background
Huntington’s disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington’s disease gene carriers (premanifest and moderate stage II/III) and controls.Methods
Control (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a), fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test.Results
We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington’s disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine) there is a suggestion (p values between 0.02 and 0.05) that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious.Conclusions
Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington’s disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington’s disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that the majority of these markers do not differ markedly by disease status. 相似文献18.
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Athan Baillet Vanessa Chanteperdrix Candice Trocmé Pierre Casez Catherine Garrel Gérard Besson 《Neurochemical research》2010,35(10):1530-1537
We examined oxidative stress markers of 31 patients suffering from ALS, 24 patients suffering from PD and 30 healthy subjects
were included. We determined the plasma levels of lipid peroxidation (malondialdehyde, MDA), of protein oxidative lesions
(plasma glutathione, carbonyls and thiols) and the activity of antioxidant enzymes i.e. erythrocyte Cu,Zn-Superoxide dismutase
(SOD), Glutathione peroxidase (GSH-Px) and catalase. MDA and thiols were significantly different in both neurodegenerative
diseases versus control population. A trend for an enhancement of oxidized glutathione was noted in ALS patients. Univariate
analysis showed that SOD activity was significantly decreased in ALS and GSH-Px activity was decreased in PD. After adjusting
for demographic parameters and enzyme cofactors, we could emphasize a compensatory increase of SOD activity in PD. Different
antioxidant systems were not involved in the same way in ALS and PD, suggesting that oxidative stress may be a cause rather
than a consequence of the neuronal death. 相似文献