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Translational Neurodegeneration

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https://www.readbyqxmd.com/read/29456842/hydrogen-sulfide-nitric-oxide-and-neurodegenerative-disorders
#1
REVIEW
Sandesh Panthi, Sumeet Manandhar, Kripa Gautam
Hydrogen Sulfide (H2 S) and Nitric Oxide (NO) have become recognized as important gaseous signaling molecules with enormous pharmacological effects, therapeutic value, and central physiological roles. NO is one of the most important regulators of the pathophysiological condition in central nervous system (CNS). It is critical in the various functioning of the brain; however, beyond certain concentration/level, it is toxic. H2 S was regarded as toxic gas with the smell like rotten egg. But, it is now regarded as emerging neuroprotectant and neuromodulator...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29423193/alzheimer-s-disease-hypothesis-and-related-therapies
#2
REVIEW
Xiaoguang Du, Xinyi Wang, Meiyu Geng
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause for dementia. There are many hypotheses about AD, including abnormal deposit of amyloid β (Aβ) protein in the extracellular spaces of neurons, formation of twisted fibers of tau proteins inside neurons, cholinergic neuron damage, inflammation, oxidative stress, etc., and many anti-AD drugs based on these hypotheses have been developed. In this review, we will discuss the existing and emerging hypothesis and related therapies...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29387348/age-induced-neuronal-cell-death-is-enhanced-in-g2019s-lrrk2-mutation-with-increased-rage-expression
#3
Hyun Jin Cho, Chengsong Xie, Huaibin Cai
Background: Leucine-rich repeat kinase 2 (LRRK2) mutations represent the most common genetic cause of sporadic and familial Parkinson's disease (PD). Especially, LRRK2 G2019S missense mutation has been identified as the most prevalent genetic cause in the late-onset PD. Advanced glycation end products (AGEs) are produced in high amounts in diabetes and diverse aging-related disorders, such as cardiovascular disease, renal disease, and neurological disease. AGEs trigger intracellular signaling pathway associated with oxidative stress and inflammation as well as cell death...
2018: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29296278/clinical-features-of-parkinson-s-disease-with-and-without-rapid-eye-movement-sleep-behavior-disorder
#4
Ye Liu, Xiao-Ying Zhu, Xiao-Jin Zhang, Sheng-Han Kuo, William G Ondo, Yun-Cheng Wu
Background: Rapid eye movement sleep behavior disorder (RBD) and Parkinson's disease (PD) are two distinct clinical diseases but they share some common pathological and anatomical characteristics. This study aims to confirm the clinical features of RBD in Chinese PD patients. Methods: One hundred fifty PD patients were enrolled from the Parkinson`s disease and Movement Disorders Center in Department of Neurology, Shanghai General Hospital from January 2013 to August 2014...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29270291/mini-review-on-initiatives-to-interfere-with-the-propagation-and-clearance-of-alpha-synuclein-in-parkinson-s-disease
#5
REVIEW
Daniel Kam Yin Chan, Ying Hua Xu, Luke Kar Man Chan, Nady Braidy, George D Mellick
In this mini-review, we summarize recent findings relating to the prion-like propagation of α-synuclein (α-syn) and the development of novel therapeutic strategies to target synucleinopathy in Parkinson's disease (PD). We link the Braak's staging hypothesis of PD with the recent evidence from in-vivo and in-vitro studies for the prion-like cell-to-cell propagation of α-syn (via exocytosis and endocytosis). The classical accumulation of aggregated α-syn in PD may result from an increased production or a failure in the mechanisms of clearance of α-syn...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29255601/identification-of-ser465-as-a-novel-pink1-autophosphorylation-site
#6
Ji-Feng Guo, Ling-Yan Yao, Qi-Ying Sun, Yi-Ting Cui, Yang Yang, Qian Xu, Xin-Xiang Yan, Bei-Sha Tang
Background: PINK1 (PTEN-induced putative kinase 1) gene is the causal gene for recessive familial type 6 of Parkinson's disease (PARK6), which is an early-onset autosomal recessive inherited neurodegenerative disease. PINK1 has been reported to exert both autophosphorylation and phosphorylation activity, affecting cell damage under stress and other physiological responses. However, there has been no report on the identification of PINK1 autophosphorylation sites and their physiological functions...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29209494/rnai-mechanisms-in-huntington-s-disease-therapy-sirna-versus-shrna
#7
REVIEW
Sebastian Aguiar, Bram van der Gaag, Francesco Albert Bosco Cortese
Huntington's Disease (HD) is a genetically dominant trinucleotide repeat disorder resulting from CAG repeats within the Huntingtin (HTT) gene exceeding a normal range (> 36 CAGs). Symptoms of the disease manifest in middle age and include chorea, dystonia, and cognitive decline. Typical latency from diagnosis to death is 20 years. There are currently no disease-modifying therapies available to HD patients. RNAi is a potentially curative therapy for HD. A popular line of research employs siRNA or antisense oligonucleotides (ASO) to knock down mutant Huntingtin mRNA (mHTT)...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29204273/specific-serum-antibody-binding-to-phosphorylated-and-non-phosphorylated-tau-in-non-cognitively-impaired-mildly-cognitively-impaired-and-alzheimer-s-disease-subjects-an-exploratory-study
#8
Andrea C Klaver, Mary P Coffey, David A Bennett, David A Loeffler
Background: Tau vaccination and administration of anti-tau antibodies can prevent pathology and cognitive impairment in transgenic mouse models of tauopathy, suggesting that therapies which increase anti-tau antibodies might slow the development and/or progression of Alzheimer's disease (AD). The extent to which individuals with no cognitive impairment (NCI) possess serum anti-tau antibodies, and whether their concentrations of these antibodies differ from anti-tau antibody levels in persons with mild cognitive impairment (MCI) or AD, are unclear...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29201361/quercetin-prevents-spinal-motor-neuron-degeneration-induced-by-chronic-excitotoxic-stimulus-by-a-sirtuin-1-dependent-mechanism
#9
Rafael Lazo-Gomez, Ricardo Tapia
Background: Excitotoxicity is a mechanism of foremost importance in the selective motor neuron degeneration characteristic of motor neuron disorders. Effective therapeutic strategies are an unmet need for these disorders. Polyphenols, such as quercetin and resveratrol, are plant-derived compounds that activate sirtuins (SIRTs) and have shown promising results in some models of neuronal death, although their effects have been scarcely tested in models of motor neuron degeneration. Methods: In this work we investigated the effects of quercetin and resveratrol in an in vivo model of excitotoxic motor neuron death induced by the chronic infusion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) into the rat spinal cord tissue...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29093814/nicorandil-potentiates-sodium-butyrate-induced-preconditioning-of-neurons-and-enhances-their-survival-upon-subsequent-treatment-with-h2o2
#10
Parisa Tabeshmehr, Haider Kh Husnain, Mahin Salmannejad, Mahsa Sani, Seyed Mojtaba Hosseini, Mohammad Hossein Khorraminejad Shirazi
Background: Extensive loss of donor neural stem cell (NSCs) due to ischemic stress and low rate of differentiation at the site of cell graft are two of the major issues that hamper optimal outcome in NSCs transplantation studies. Given that histone deacetylases (HDACs) modulate various cellular processes by deacetylating histones and non-histone proteins, we hypothesized that combined treatment with small molecules, sodium butyrate (NaB; a known HDAC inhibitor) and nicorandil, will enhance the rate neuronal differentiation of NSCs besides their preconditioning to resist oxidative stress...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29090092/current-understanding-of-the-molecular-mechanisms-in-parkinson-s-disease-targets-for-potential-treatments
#11
REVIEW
Panchanan Maiti, Jayeeta Manna, Gary L Dunbar
Gradual degeneration and loss of dopaminergic neurons in the substantia nigra, pars compacta and subsequent reduction of dopamine levels in striatum are associated with motor deficits that characterize Parkinson's disease (PD). In addition, half of the PD patients also exhibit frontostriatal-mediated executive dysfunction, including deficits in attention, short-term working memory, speed of mental processing, and impulsivity. The most commonly used treatments for PD are only partially or transiently effective and are available or applicable to a minority of patients...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29046784/the-role-of-gene-variants-in-the-pathogenesis-of-neurodegenerative-disorders-as-revealed-by-next-generation-sequencing-studies-a-review
#12
REVIEW
Shirley Yin-Yu Pang, Kay-Cheong Teo, Jacob Shujui Hsu, Richard Shek-Kwan Chang, Miaoxin Li, Pak-Chung Sham, Shu-Leong Ho
The clinical diagnosis of neurodegenerative disorders based on phenotype is difficult in heterogeneous conditions with overlapping symptoms. It does not take into account the disease etiology or the highly variable clinical course even amongst patients diagnosed with the same disorder. The advent of next generation sequencing (NGS) has allowed for a system-wide, unbiased approach to identify all gene variants in the genome simultaneously. With the plethora of new genes being identified, genetic rather than phenotype-based classification of Mendelian diseases such as spinocerebellar ataxia (SCA), hereditary spastic paraplegia (HSP) and Charcot-Marie-Tooth disease (CMT) has become widely accepted...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/29021896/disease-modification-and-neuroprotection-in-neurodegenerative-disorders
#13
REVIEW
Jeffrey Cummings
BACKGROUND: Disease modifying therapies (DMTs) are urgently needed for neurodegenerative diseases (NDD) such as Alzheimer's disease (AD) and many other disorders characterized by protein aggregation and neurodegeneration. Despite advances in understanding the neurobiology of NDD, there are no approved DMTs. DISCUSSION: Defining disease-modification is critical to drug-development programs. A DMT is an intervention that produces an enduring change in the trajectory of clinical decline of an NDD by impacting the disease processes leading to nerve cell death...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28932391/photophobia-in-neurologic-disorders
#14
REVIEW
Yiwen Wu, Mark Hallett
Photophobia is a common symptom seen in many neurologic disorders, however, its pathophysiology remains unclear. Even the term is ambiguous. In this paper, we review the epidemiology and clinical manifestations of photophobia in neurological disorders, including primary headache, blepharospasm, progressive supranuclear palsy, and traumatic brain injury, discuss the definition, etiology and pathogenesis, and summarize practical methods of diagnosis and treatment.
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28919975/mild-cognitive-impairment-in-parkinson-s-disease-a-distinct-clinical-entity
#15
REVIEW
Ming-Ching Wen, Ling Ling Chan, Louis C S Tan, Eng King Tan
BACKGROUND: Mild cognitive impairment in Parkinson's disease (PD-MCI) is a common clinical condition. Understanding its pathology and clinical features is important for early intervention before the onset of dementia. In the past, variable definitions and differences in neuropsychological batteries generated divergent results of the affected cognitive patterns. MAIN BODY: The introduction of PD-MCI criteria by the Movement Disorders Society (MDS) Task Force provides a more uniform system for defining and measuring PD-MCI and may improve the validity of future research...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28855981/role-of-bace1-in-alzheimer-s-synaptic-function
#16
REVIEW
Brati Das, Riqiang Yan
Alzheimer's disease (AD) is the most common age-dependent disease of dementia, and there is currently no cure available. This hallmark pathologies of AD are the presence of amyloid plaques and neurofibrillary tangles. Although the exact etiology of AD remains a mystery, studies over the past 30 have shown that abnormal generation or accumulation of β-amyloid peptides (Aβ) is likely to be a predominant early event in AD pathological development. Aβ is generated from amyloid precursor protein (APP) via proteolytic cleavage by β-site APP cleaving enzyme 1 (BACE1)...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28852477/endoplasmic-reticulum-mitochondria-tethering-in-neurodegenerative-diseases
#17
REVIEW
Yi Liu, Xiongwei Zhu
Endoplasmic reticulum (ER) and mitochondria are tubular organelles with a characteristic "network structure" that facilitates the formation of inter-organellar connections. As a result, mitochondria-associated ER membranes (MAMs), a subdomain of the ER that is tightly linked to and communicates with mitochondria, serve multiple physiological functions including lipid synthesis and exchange, calcium signaling, bioenergetics, and apoptosis. Importantly, emerging evidence suggests that the abnormality and dysfunction of MAMs have been involved in various neurodegenerative disorders including Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28824801/the-role-of-amyloid-beta-clearance-in-cerebral-amyloid-angiopathy-more-potential-therapeutic-targets
#18
REVIEW
Xue-Mei Qi, Jian-Fang Ma
Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid β-protein (Aβ) in the leptomeningeal and cortical blood vessels, which is an age-dependent risk factor for intracerebral hemorrhage (ICH), ischemic stroke and contributes to cerebrovascular dysfunction leading to cognitive impairment. However clinical prevention and treatment of the disease is very difficult because of its occult onset and severity of the symptoms. In recent years, many anti-amyloid β immunotherapies have not demonstrated clinical efficacy in subjects with Alzheimer's disease (AD), and the failure may be due to the deposition of Aβ in the cerebrovascular export pathway resulting in further damage to blood vessels and aggravating CAA...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28702179/pathological-correlations-between-traumatic-brain-injury-and-chronic-neurodegenerative-diseases
#19
REVIEW
Marcela Cruz-Haces, Jonathan Tang, Glen Acosta, Joseph Fernandez, Riyi Shi
Traumatic brain injury is among the most common causes of death and disability in youth and young adults. In addition to the acute risk of morbidity with moderate to severe injuries, traumatic brain injury is associated with a number of chronic neurological and neuropsychiatric sequelae including neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, despite the high incidence of traumatic brain injuries and the established clinical correlation with neurodegeneration, the causative factors linking these processes have not yet been fully elucidated...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28702178/the-development-prospection-of-hdac-inhibitors-as-a-potential-therapeutic-direction-in-alzheimer-s-disease
#20
REVIEW
Shuang-Shuang Yang, Rui Zhang, Gang Wang, Yong-Fang Zhang
Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is associated with learning and memory impairment in the elderly. Recent studies have found that treating AD in the way of chromatin remodeling via histone acetylation is a promising therapeutic regimen. In a number of recent studies, inhibitors of histone deacetylase (HDACs) have been found to be a novel promising therapeutic agents for neurological disorders, particularly for AD and other neurodegenerative diseases. Although HDAC inhibitors have the ability to ameliorate cognitive impairment, successful treatments in the classic AD animal model are rarely translated into clinical trials...
2017: Translational Neurodegeneration
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