Developing biomarkers for neurodegenerative diseases using genetically-modified common marmoset models

正Mouse and non-human primate models of neurodegenerative disease:The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60.Although the difficulties associated with neurodegenerative diseases present an urgent global issue,there is no effective treatment for these conditions.To develop therapeutic methods and therapeutic agents for neurodegenerative diseases,model animals     

Current controversies in glia-to-neuron conversion therapy in neurodegenerative diseases

<正>Loss of neurons and disruption of neural circuits are associated with many neurological diseases,including neurodegenerative diseases and mental disorders.The most prevalent pathological feature of neurodegenerative diseases is the aggregate loss of certain neuronal populations.     

Stem cell therapy in neurodegenerative diseases From principles to practice

The lack of curative therapies for neurodegenerative diseases has high economic impact and places huge burden on the society.The contribution of stem cells to cure neurodegenerative diseases has been unraveled and explored extensively over the past few years.Beyond substitution of the lost neurons,stem cells act as immunomodulators and neuroprotectors.A large number of preclinical and a small number of clinical studies have shown beneficial outcomes in this context.In this review,we have summarized the current concepts of stem cell therapy in neurodegenerative diseases and the recent advances in this field,particularly between 2010 and 2012.Further studies should be encouraged to resolve the clinical issues and vague translational findings for maximum optimization of the efficacy of stem cell therapy in neurodegenerative diseases.     

Human survival and immune mediated mitophagy in neuroplasticity disorders

<正>Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with complex factors such as neurohumoral,endocrine and environmental factors involved in induction of these neurodegenerative diseases.The future of science and medicine in neurodegenerative diseases is now     

Oxidative stress, mitochondrial damage and neurodegenerative diseases****

Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca2＋ homeostasis and mitochondrial defense systems. All these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative diseases and discusses strategies to modify mitochondrial dysfunction that may be attractive therapeutic interventions for the treatment of various neurodegenerative diseases.     

Food,polyphenols and neuroprotection

<正>Neuron loss and neurodegeneration are the common denominators of what are known as neurodegenerative diseases.Although the clinical manifestations of some neurodegenerative diseases are mainly associated with ageing,it is believed that onset of disease and neuronal death occurs progressively through life,well before the first symptoms appear.So,one of the main dilemmas regarding neurodegenerative disease ther-     

Advanced diffusion magnetic resonance imaging in patients with Alzheimer’s and Parkinson’s diseases

The prevalence of neurodegenerative diseases is increasing as human longevity increases. The objective biomarkers that enable the staging and early diagnosis of neurodegenerative diseases are eagerly anticipated. It has recently become possible to determine pathological changes in the brain without autopsy with the advancement of diffusion magnetic resonance imaging techniques. Diffusion magnetic resonance imaging is a robust tool used to evaluate brain microstructural complexity and integrity, axonal order, density, and myelination via the micron-scale displacement of water molecules diffusing in tissues. Diffusion tensor imaging, a type of diffusion magnetic resonance imaging technique is widely utilized in clinical and research settings;however, it has several limitations. To overcome these limitations, cutting-edge diffusion magnetic resonance imaging techniques, such as diffusional kurtosis imaging, neurite orientation dispersion and density imaging, and free water imaging, have been recently proposed and applied to evaluate the pathology of neurodegenerative diseases. This review focused on the main applications, findings, and future directions of advanced diffusion magnetic resonance imaging techniques in patients with Alzheimer's and Parkinson's diseases, the first and second most common neurodegenerative diseases, respectively.     

THE MITOCHONDRIAL DERANGEMENTS IN NEURONAL DEGENER ATION AND NEURODEGENERATIVE DISEASES

There are diverse concepts on the pathogenesis of neuronal degeneration and the neurodegenerative diseases. Among them there are different factors which might influence the initiation of neuronal degeneration as well as the pathogenesis of neurodegenerative diseases, such as Alzheimer′s disease, Parkinson′s disease, motor neuron disease, and so on.     

Targeting prion-like protein spreading in neurodegenerative diseases

The infectious template-mediated protein conversion is a unique mechanism for the onset of rare and fatal neurodegenerative disorders known as transmissible spongiform encephalopathies, or prion diseases, which affect humans and other animal species. However, emerging studies are now demonstrating prion-like mechanisms of self-propagation of protein misfolding in a number of common, non-infectious neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. It has been proposed that distinct and unrelated proteins(beta-amyloid, tau, α-synuclein, TAR DNA-binding protein 43 and huntingtin, etc.) associated with common neurodegenerative disorders can seed conversion and spread via cellto-cell transfer, sustaining the transmission of neurotoxic agents along a stereotypic route, sharing features at the heart of the intrinsic nature of prions. Here we review the most recent development on both the molecular mechanisms underlying the pathogenesis of prion-like neurodegenerative diseases as well as innovative methods and strategies for potential therapeutic applications.     

Autophagy and its neuroprotection in neurodegenerative diseases

It has been suggested that protein misfolding and aggregation contribute significantly to the development of neurodegenerative diseases.Misfolded and aggregated proteins are cleared by ubiquitin proteasomal system (UPS) and by both Micro and Macro autophagy lysosomal pathway (ALP).Autophagosomal dysfunction has been implicated in an increasing number of diseases including neurodegenerative diseases.Autophagy is a cellular self-eating process that plays an important role in neuroprotection as well as neuronal injury and death.While a decrease in autophagic activity interferes with protein degradation and possibly organelle turnover,increased autophagy has been shown to facilitate the clearance of aggregation-prone proteins and promote neuronal survival in a number of disease models.On the other hand,too much autophagic activity can be detrimental,suggesting the regulation of autophagy is critical in dictating cell fate.In this review paper,we will discuss various aspects of ALP biology and its dual functions in neuronal cell death and survival.We will also evaluate the role of autophagy in neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,amyotrophic lateral sclerosis.Finally,we will explore the therapeutic potential of autophagy modifiers in several neurodegenerative diseases.     

Metabolism,neurodegeneration and epigenetics: emerging role of Sirtuins

正Along with the progressive aging of the population,the prevalence of obesity,metabolic diseases and neurodegenerative disorders continues to grow.Moreover,increasing evidence suggests that metabolic alterations strongly influence the initiation and progression of neurodegenerative disorders.Accordingly,brain aging is accompanied by metabolic,morphological and neurophysiological changes leading to the development of neurodegenerative diseases like Alzheimer’s disease(AD),Parkinson’s disease(PD),Huntington’s disease(HD)and multiple sclerosis(Procaccini et al.,2016).Since each of these disorders involve impaired energy metabolism and/or adverse changes in the ce-     

Neuroprotective effects of berry fruits on neurodegenerative diseases

Recent clinical research has demonstrated that berry fruits can prevent age-related neurodegenerative diseases and improve motor and cognitive functions. The berry fruits are also capable of modulating signaling pathways involved in inflammation, cell survival, neurotransmission and enhancing neuroplasticity. The neuroprotective effects of berry fruits on neurodegenerative diseases are related to phytochemicals such as anthocyanin, caffeic acid, catechin, quercetin, kaempferol and tannin. In this review, we made an attempt to clearly describe the beneficial effects of various types of berries as promising neuroprotective agents.     

Role of the NLRP3 inflammasome in neurodegenerative diseases and therapeutic implications

Neurodegenerative diseases are a group of neuronal disorders caused by progressive neuronal cell death in different regions of the human brain.Alzheimer's disease(AD)and Parkinson's disease(PD)are the most common types of neurodegenerative diseases that affect millions of people worldwide.There is no cure available for either disease.One of the pathological hallmarks of neurodegenerative diseases is the abnormal protein aggregation in the central nervous system.     

Application of flavonoids for the protection of nigral dopaminergic neurons from oxidative stress

正Oxidative stress in Parkinson's disease(PD): Oxidative stress is the imbalance between oxidants, which generate reactive oxygen species(ROS; free radicals), and antioxidants, which remove free radicals.Under healthy conditions, the levels of oxidants and antioxidants are wellbalanced.However, excessive production of ROS and a deficiency of antioxidants leads to oxidative stress, which may be the cause of accelerating the development of neurodegenerative diseases(Hwang, 2013), suggesting that the prevention of ROS production and reduction of oxidative stress is critical for both the prevention and treatment of neurodegenerative diseases, including PD.     

Blood exosomes as a tool for monitoring treatment efficacy and progression of neurodegenerative diseases

<正>Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,amyotrophic lateral sclerosis,and prion disease are representative neurodegenerative diseases that share common sub-cellular features,the most obvious of which is a strong association with the accumulation of misfolded,aggregated,and insoluble forms of proteins in the brain,as evidenced in post-mortem brain tissues of patients.Diagnosis of neurodegenerative diseases is often made     

Free ubiquitin: a novel therapeutic target for neurodegenerative diseases

正Neurodegenerative diseases are widespread and the increasing number of patients with these diseases can no longer be ignored. Dementia is a symptom of many neurodegenerative diseases, and Alzheimer's disease(AD), which is associated with memory and learning disabilities, accounts for approximately 60 to 80% of all dementia cases(Wyss-Coray, 2016).     

Beneficial effects of AAV1-Rheb(S16H) administration in the adult hippocampus

Neurotrophic factors against neurodegenerative diseases such as Alzheimer’s disease(AD)and Parkinson’s disease(PD):A clear understanding of the etiology of neurodegenerative diseases,such as AD and PD remains elusive.Although there is still no therapy to prevent or block neurodegeneration,in vivo and in vitro experimental results have shown that the direct administration of neurotrophic factors,such as brain-derived neurotrophic factor(BDNF)and ciliary neurotrophic factor(CNTF),and the induction of these neurotrophic factors via specific gene delivery may protect neurons against neurotoxicity in neurodegenerative disease models(Kim et al.,2012;Jeong et al.,2013,2015).     

Possible protective action of neurotrophic factors and natural compounds against common neurodegenerative diseases

It has been suggested that altered levels/function of brain-derived neurotrophic factor （BDNF） play a role in the pathophysiology of neurodegenerative diseases including Alzheimer＇s disease. BDNF positively contributes to neural survival and synapse maintenance via stimulating its high affinity receptor TrkB, making upregulation of BDNF and/or activation of BDNF-related intracellnlar signaling an attractive approach to treating neurodegenerative diseases. In this short review, I briefly introduce small natural compounds such as flavonoids that successfully increase activation of the BDNF system and discuss their beneficial effects against neurodegeneration.     

Natural polyphenols effects on protein aggregates in Alzheimer's and Parkinson's prion-like diseases

Alzheimer's and Parkinson's diseases are the most common neurodegenerative diseases. They are characterized by protein aggregates and so can be considered as prion-like disease. The major components of these deposits are amyloid peptide and tau for Alzheimer's disease, α-synuclein and synphilin-1 for Parkinson's disease. Drugs currently proposed to treat these pathologies do not prevent neurodegenerative processes and are mainly symptomatic therapies. Molecules inducing inhibition of aggregation or disaggregation of these proteins could have beneficial effects, especially if they have other beneficial effects for these diseases. Thus, several natural polyphenols, which have antioxidative, anti-inflammatory and neuroprotective properties, have been largely studied, for their effects on protein aggregates found in these diseases, notably in vitro. In this article, we propose to review the significant papers concerning the role of polyphenols on aggregation and disaggregation of amyloid peptide, tau, α-synuclein, synphilin-1, suggesting that these compounds could be useful in the treatments in Alzheimer's and Parkinson's diseases.