Neuroprotective Effects of Heat-Killed Lactobacillus plantarum 200655 Isolated from Kimchi Against Oxidative Stress

Probiotics and Antimicrobial Proteins - Oxidative stress plays an important role in exacerbating neurodegenerative diseases, such as Alzheimer's disease, Parkinson’s disease, and...     

Cytoplasmic dynein: a key player in neurodegenerative and neurodevelopmental diseases

Cytoplasmic dynein is the most important molecular motor driving the movement of a wide range of cargoes towards the minus ends of microtubules.As a molecular motor protein,dynein performs a variety of basic cellular functions including organelle transport and centrosome assembly.In the nervous system,dynein has been demonstrated to be responsible for axonal retrograde transport.Many studies have revealed direct or indirect evidence of dynein in neurodegenerative diseases such as amyotrophic lateral sclerosis,Charcot-Marie-Tooth disease,Alzheimer’s disease,Parkinson’s disease and Huntington’s disease.Among them,a number of mutant proteins involved in various neurodegenerative diseases interact with dynein.Axonal transport disruption is presented as a common feature occurring in neurodegenerative diseases.Dynein heavy chain mutant mice also show features of neurodegenerative diseases.Moreover,defects of dynein-dependent processes such as autophagy or clearance of aggregation-prone proteins are found in most of these diseases.Lines of evidence have also shown that dynein is associated with neurodevelopmental diseases.In this review,we focus on dynein involvement in different neurological diseases and discuss potential underlying mechanisms.     

Idebenone Ameliorates Rotenone-Induced Parkinson’s Disease in Rats Through Decreasing Lipid Peroxidation

Neurochemical Research - Oxidative stress is considered one of the mechanisms responsible for neurodegenerative diseases, especially for Parkinson’s disease. Since oxidative stress causes...     

Autophagy of Mitochondria: A Promising Therapeutic Target for Neurodegenerative Disease

The autophagic process is the only known mechanism for mitochondrial turnover and it has been speculated that dysfunction of autophagy may result in mitochondrial error and cellular stress. Emerging investigations have provided new understanding of how autophagy of mitochondria (also known as mitophagy) is associated with cellular oxidative stress and its impact on neurodegeneration. This impaired autophagic function may be considered as a possible mechanism in the pathogenesis of several neurodegenerative disorders including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease. It can be suggested that autophagy dysfunction along with oxidative stress is considered main events in neurodegenerative disorders. New therapeutic approaches have now begun to target mitochondria as a potential drug target. This review discusses evidence supporting the notion that oxidative stress and autophagy are intimately associated with neurodegenerative disease pathogenesis. This review also explores new approaches that can prevent mitochondrial dysfunction, improve neurodegenerative etiology, and also offer possible cures to the aforementioned neurodegenerative diseases.     

Resistin-Inhibited Neural Stem Cell-Derived Astrocyte Differentiation Contributes to Permeability Destruction of the Blood–Brain Barrier

Neurochemical Research - Neuroinflammation is an important part of the development of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s and amyotrophic lateral...     

The role of NADPH oxidase (NOX) enzymes in neurodegenerative disease

Recently, mounting evidence implicating reactive oxygen species (ROS) generated by NADPH oxidase (NOX) enzymes in the pathogenesis of several neurodegenerative diseases including Amyotrophic lateral sclerosis (ALS), Alzheimer’s (AD), Parkinson’s (PD) and polyglutamine disease, have arisen. NOX enzymes are transmembrane proteins and generate reactive oxygen species by transporting electrons across lipid membranes. Under normal healthy conditions, low levels of ROS produced by NOX enzymes have been shown to play a role in neuronal differentiation and synaptic plasticity. However, in chronic neurodegenerative diseases over-activation of NOX in neurons, as well as in astrocytes and microglia, has been linked to pathogenic processes such as oxidative stress, exitotoxicity and neuroinflammation. In this review, we summarize the current knowledge about NOX functions in the healthy central nervous system and especially the role of NOX enzymes in neurodegenerative disease processes.     

Shared mechanisms among neurodegenerative diseases: from genetic factors to gene networks

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are pressing health concerns in modern societies for which effective therapies are still lacking. Recent high-throughput genomic technologies have enabled genome-scale, multidimensional investigations to facilitate a better understanding of the underlying mechanisms and the identification of novel targets. Here we review the molecular insights gained through such studies, and compare the similarities and differences between neurodegenerative diseases revealed by systems genomics and gene network modelling approaches. We focus specifically on the shared mechanisms at multiple molecular scales ranging from genetic factors to gene expression to network-level features of gene regulation, and whenever possible also point out mechanisms that distinguish one disease from another. Our review sets the stage for similar genomewide inspection in the future on shared/distinct features of neurodegenerative diseases at the levels of cellular, proteomic or epigenomic signatures, and how these features may interact to determine the progression and treatment response of different diseases afflicting the same individual.     

溶酶体离子通道蛋白在神经退行性疾病发生发展中的作用及机制研究

溶酶体离子通道蛋白异常引起溶酶体功能障碍是导致阿尔茨海默病(Alzheimer’s disease,AD)和帕金森病(Parkinson’s disease,PD)等神经退行性疾病的重要因素.溶酶体离子通道蛋白调节溶酶体内离子稳态、溶酶体膜电压以及溶酶体的酸度.溶酶体离子通道蛋白的结构或功能缺陷会引起溶酶体降解功能障碍,导致神经退行性疾病的发生发展.在这篇综述中,我们总结了各种离子通道蛋白调节溶酶体功能的过程及机制,以及离子通道蛋白异常参与神经退行性疾病的过程和机制.调节离子通道蛋白改善溶酶体的功能、促进异常聚集蛋白的清除,是神经退行性疾病治疗的潜在途径.     

The neurotoxicity of iron,copper and cobalt in Parkinson’s disease through ROS-mediated mechanisms

Parkinson’s disease (PD) is the second most common neurodegenerative disease with gradual loss of dopaminergic neurons. Despite extensive research in the past decades, the etiology of PD remains elusive. Nevertheless, multiple lines of evidence suggest that oxidative stress is one of the common causes in the pathogenesis of PD. It has also been suggested that heavy metal-associated oxidative stress may be implicated in the etiology and pathogenesis of PD. Here we review the roles of redox metals, including iron, copper and cobalt, in PD. Iron is a highly reactive element and deregulation of iron homeostasis is accompanied by concomitant oxidation processes in PD. Copper is a key metal in cell division process, and it has been shown to have an important role in neurodegenerative diseases such as PD. Cobalt induces the generation of reactive oxygen species (ROS) and DNA damage in brain tissues.     

Neuropeptide Y mitigates ER stress–induced neuronal cell death by activating the PI3K–XBP1 pathway

The unfolded protein response (UPR) is an evolutionarily conserved adaptive reaction that increases cell survival under endoplasmic reticulum (ER) stress conditions. ER stress–associated neuronal cell death pathways play roles in the pathogenesis of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s disease. Neuropeptide Y (NPY) has an important role in neuroprotection against neurodegenerative diseases. In this study, we investigated whether NPY has a protective role in ER stress–induced neuronal cell death in SK-N-SH human neuroblastoma cells. An ER stress–inducing chemical, tunicamycin, increased the activities of caspase-3 and -4, whereas pretreatment with NPY decreased caspase-3 and -4 activities during the ER stress response. In addition, NPY suppressed the activation of three major ER stress sensors during the tunicamycin-induced ER stress response. NPY-mediated activation of PI3K increased nuclear translocation of XBP1s, which in turn induced expression of Grp78/BiP. Taken together, our data indicated that NPY plays a protective role in ER stress–induced neuronal cell death through activation of the PI3K–XBP1 pathway, and that NPY signaling can serve as therapeutic target for ER stress–mediated neurodegenerative diseases.     

内质网应激与帕金森病

内质网是细胞内最重要的细胞器之一,内质网功能与细胞状态密切相关。异常蛋白在内质网的堆积、胆固醇代谢异常、钙代谢紊乱等均能引起内质网应激。内质网应激在细胞生理病理中发挥重要作用。研究表明:内质网应激与神经退行性疾病,如帕金森病密切相关。该文简单概述了内质网应激与帕金森病之间的关系。     

Retinol (Vitamin A) Increases α-Synuclein, β-Amyloid Peptide,Tau Phosphorylation and RAGE Content in Human SH-SY5Y Neuronal Cell Line

Retinoids (vitamin A and derivatives) are recognized as essential factors for central nervous system (CNS) development. Retinol (vitamin A) also was postulated to be a major antioxidant component of diet as it modulates reactive species (RS) production and oxidative stress in biological systems. Oxidative stress plays a major role either in pathogenesis or development of neurodegenerative diseases, or even in both. Here we investigate the role of retinol supplementation to human neuron-derived SH-SY5Y cells over RS production and biochemical markers associated to neurodegenerative diseases expressed at neuronal level in Parkinson’s disease and Alzheimer’s disease: α-synuclein, β-amyloid peptide, tau phosphorylation and RAGE. Retinol treatment (24 h) impaired cell viability and increased intracellular RS production at the highest concentrations (7 up to 20 µM). Antioxidant co-treatment (Trolox 100 µM) rescued cell viability and inhibited RS production. Furthermore, retinol (10 µM) increased the levels of α-synuclein, tau phosphorylation at Ser396, β-amyloid peptide and RAGE. Co-treatment with antioxidant Trolox inhibited the increased in RAGE, but not the effect of retinol on α-synuclein, tau phosphorylation and β-amyloid peptide accumulation. These data indicate that increased availability of retinol to neurons at levels above the cellular physiological concentrations may induce deleterious effects through diverse mechanisms, which include oxidative stress but also include RS-independent modulation of proteins associated to progression of neuronal cell death during the course of neurodegenerative diseases.     

Coenzyme Q treatment of neurodegenerative diseases of aging

The etiology of several neurodegenerative disorders is thought to involve impaired mitochondrial function and oxidative stress. Coenzyme Q-10 (CoQ₁₀) acts both as an antioxidant and as an electron acceptor at the level of the mitochondria. In several animal models of neurodegenerative diseases including amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease, CoQ₁₀ has shown beneficial effects. Based on its biochemical properties and the effects in animal models, several clinical trials evaluating CoQ₁₀ have been undertaken in many neurodegenerative diseases. CoQ₁₀ appears to be safe and well tolerated, and several efficacy trials are planned.     

Free radical processes in aging, neurodegenerative diseases and other pathological states

Literature data on the role of oxidative stress in aging have been summarized. There are certain links between parameters of free radical processes (intensity of generation of reactive oxygen species in mitochondria, oxidative modification of mitochondrial DNA, activity of desaturases, involved into biosynthesis of polyunsaturated C₂₀ and C₂₂ fatty acids) with life span. The review highlights the role of oxidative stress as on of pathogenic factors of numerous diseases including various neurodegenerative disorders. Special attention is paid to oxidative modification of proteins as one of early and reliable markers of tissue injury in free radical pathology. Oxidative destruction of proteins plays a major role in etiology of such neurodegenerative diseases as Alzheimer’s and Parkinson’s diseases. Oxidative stress and the stress related protein aggregation are considered as the pathogenic link in the development of familiar amyotrophic lateral sclerosis. Oxidative modification of proteins is associated with the development of cataract. The age-and pathology-related increases in the content of oxidized proteins in tissues is assessed as an early and specific parameter of oxidative stress.     

Mitochondria and Neurodegeneration

Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. However, despite the evidence of morphological, biochemical and molecular abnormalities in mitochondria in various tissues of patients with neurodegenerative disorders, the question “is mitochondrial dysfunction a necessary step in neurodegeneration?” is still unanswered. In this review, we highlight some of the major neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease) and discuss the role of the mitochondria in the pathogenetic cascade leading to neurodegeneration.     

Microtubule-stabilizing agents as potential therapeutics for neurodegenerative disease

Microtubules (MTs), cytoskeletal elements found in all mammalian cells, play a significant role in cell structure and in cell division. They are especially critical in the proper functioning of post-mitotic central nervous system neurons, where MTs serve as the structures on which key cellular constituents are trafficked in axonal projections. MTs are stabilized in axons by the MT-associated protein tau, and in several neurodegenerative diseases, including Alzheimer’s disease, frontotemporal lobar degeneration, and Parkinson’s disease, tau function appears to be compromised due to the protein dissociating from MTs and depositing into insoluble inclusions referred to as neurofibrillary tangles. This loss of tau function is believed to result in alterations of MT structure and function, resulting in aberrant axonal transport that likely contributes to the neurodegenerative process. There is also evidence of axonal transport deficiencies in other neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington’s disease, which may result, at least in part, from MT alterations. Accordingly, a possible therapeutic strategy for such neurodegenerative conditions is to treat with MT-stabilizing agents, such as those that have been used in the treatment of cancer. Here, we review evidence of axonal transport and MT deficiencies in a number of neurodegenerative diseases, and summarize the various classes of known MT-stabilizing agents. Finally, we highlight the growing evidence that small molecule MT-stabilizing agents provide benefit in animal models of neurodegenerative disease and discuss the desired features of such molecules for the treatment of these central nervous system disorders.     

Does any drug to treat cancer target mTOR and iron hemostasis in neurodegenerative disorders?

The prevalence of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are increased by age. Alleviation of their symptoms and protection of normal neurons against degeneration are the main aspects of the research to establish novel therapeutic strategies. Iron as the one of most important cation not only play important role in the structure of electron transport chain proteins but also has pivotal duties in cellular activities. But disruption in iron hemostasis can make it toxin to neurons which causes lipid peroxidation, DNA damage and etc. In patients with Alzheimer and Parkinson misbalancing in iron homeostasis accelerate neurodegeneration and cause neuroinflmmation. mTOR as the common signaling pathway between cancer and neurodegenerative disorders controls iron uptake and it is in active form in both diseases. Anti-cancer drugs which target mTOR causes iron deficiency and dual effects of mTOR inhibitors can candidate them as a therapeutic strategy to alleviate neurodegeneration/inflammation because of iron overloading.     

Long-term effects of ionising radiation on the brain: cause for concern?

There is no clear evidence proving or disproving that ionising radiation is causally linked with neurodegenerative diseases such as Parkinson’s and Alzheimer’s. However, it is known that high doses of ionising radiation to the head (20–50 Gy) lead to severe learning and memory impairment which is characteristical for Alzheimer’s. The cumulative doses of ionising radiation to the Western population are accruing, mostly due to the explosive growth of medical imaging procedures. Children are in particular prone to ionising radiation as the molecular processes within the brain are not completely finished. Furthermore, they have a long lifespan under risk. We wish to open a debate if such low doses of radiation exposure may lead to delayed long-term cognitive and other defects, albeit at a lower frequency than those observed during application of high doses. Further, we want to sensitise the society towards the risks of ionising radiation. To achieve these aims, we will recapitulate the known symptoms of Parkinson’s and Alzheimer’s on the molecular level and incorporate data of mainly low- and moderate-ionising radiation (<5 Gy). Thus, we want to highlight in general the potential similarities of both the neurodegenerative and radiation-induced pathways. We will propose a mechanistic model for radiation-induced neurodegeneration pointing out mitochondria as a key element. This includes effects of oxidative stress and neuroinflammation—all fundamental players of neurodegenerative diseases.