抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

For a long time, superoxide generation by an NADPH oxidase was considered as an oddity only found in professional phagocytes. Over the last years, six homologs of the cytochrome subunit of the phag...

/pdf/the-nox-family-of-ros-generating-nadph-oxidases-physiology-zjc88zvh59.pdf

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

There is an increasing amount of experimental evidence that oxidative stress is a causal, or at least an ancillary, factor in the neuropathology of several adult neurodegenerative disorders, as well as in stroke, trauma, and seizures. At the same time, excessive or persistent activation of glutamate-gated ion channels may cause neuronal degeneration in these same conditions. Glutamate and related acidic amino acids are thought to be the major excitatory neurotransmitters in brain and may be utilized by 40 percent of the synapses. Thus, two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain. The broad distribution in brain of the processes regulating oxidative stress and mediating glutamatergic neurotransmission may explain the wide range of disorders in which both have been implicated. Yet differential expression of components of the processes in particular neuronal systems may account for selective neurodegeneration in certain disorders.

https://science.sciencemag.org/content/sci/262/5134/689.full.pdf

Oxidative stress, glutamate, and neurodegenerative disorders

Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Despite scepticism concerning its bioavailability, a growing body of in vivo evidence indicates that resveratrol has protective effects in rodent models of stress and disease. Here, we provide a comprehensive and critical review of the in vivo data on resveratrol, and consider its potential as a therapeutic for humans.

Therapeutic potential of resveratrol: the in vivo evidence.

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Resveratrol protects against global cerebral ischemic injury in gerbils.

The "French Paradox" and beyond: neuroprotective effects of polyphenols

Neuronal excitation involving the excitatory glutamate receptors is recognized as an important underlying mechanism in neurodegenerative disorders. Excitation resulting from stimulation of the ionotropic glutamate receptors is known to cause the increase in intracellular calcium and trigger calcium-dependent pathways that lead to neuronal apoptosis. Kainic acid (KA) is an agonist for a subtype of ionotropic glutamate receptor, and administration of KA has been shown to increase production of reactive oxygen species, mitochondrial dysfunction, and apoptosis in neurons in many regions of the brain, particularly in the hippocampal subregions of CA1 and CA3, and in the hilus of dentate gyrus (DG). Systemic injection of KA to rats also results in activation of glial cells and inflammatory responses typically found in neurodegenerative diseases. KA-induced selective vulnerability in the hippocampal neurons is related to the distribution and selective susceptibility of the AMPA/kainate receptors in the brain. Recent studies have demonstrated ability of KA to alter a number of intracellular activities, including accumulation of lipofuscin-like substances, induction of complement proteins, processing of amyloid precursor protein, and alteration of tau protein expression. These studies suggest that KA-induced excitotoxicity can be used as a model for elucidating mechanisms underlying oxidative stress and inflammation in neurodegenerative diseases. The focus of this review is to summarize studies demonstrating KA-induced excitotoxicity in the central nervous system and possible intervention by anti-oxidants.

Kainic acid-mediated excitotoxicity as a model for neurodegeneration.

Parkinson’s disease (PD) is the second most prevalent age-related neurodegenerative disease with physiological manifestations including tremors, bradykinesia, abnormal postural reflexes, rigidity and akinesia and pathological landmarks showing losses of dopaminergic neurons in the substantia nigra. Although the etiology of PD has been intensively pursued for several decades, biochemical mechanisms and genetic and epigenetic factors leading to initiation and progression of the disease remain elusive. Environmental toxins including (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) MPTP, paraquat and rotenone have been shown to increase the risk of PD in humans. Oxidative stress remains the leading theory for explaining progression of PD. Studies with cell and animal models reveal oxidative and inflammatory properties of these toxins and their ability to activate glial cells which subsequently destroy neighboring dopaminergic neurons. This review describes pathological effects of neurotoxins on cells and signaling pathways for production of reactive oxygen species (ROS) that underline the pathophysiology of PD.

Oxidative and Inflammatory Pathways in Parkinson's Disease

Excess production of reactive oxygen species in the brain has been implicated as a common underlying risk factor for the pathogenesis of a number of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In recent years, there is considerable interest concerning investigation of antioxidative and anti-inflammatory effects of phenolic compounds from different botanical sources. In this review, we first describe oxidative mechanisms associated with stroke, AD, and PD, and subsequently, we place emphasis on recent studies implicating neuroprotective effects of resveratrol, a polyphenolic compound derived from grapes and red wine. These studies show that the beneficial effects of resveratrol are not only limited to its antioxidant and anti-inflammatory action but also include activation of sirtuin 1 (SIRT1) and vitagenes, which can prevent the deleterious effects triggered by oxidative stress. In fact, SIRT1 activation by resveratrol is gaining importance in the development of innovative treatment strategies for stroke and other neurodegenerative disorders. The goal here is to provide a better understanding of the mode of action of resveratrol and its possible use as a potential therapeutic agent to ameliorate stroke damage as well as other age-related neurodegenerative disorders.

Albert Y. Sun

Papers

Resveratrol protects against global cerebral ischemic injury in gerbils.

The "French Paradox" and beyond: neuroprotective effects of polyphenols

Kainic acid-mediated excitotoxicity as a model for neurodegeneration.

Oxidative and Inflammatory Pathways in Parkinson's Disease

Resveratrol as a Therapeutic Agent for Neurodegenerative Diseases