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Alzheimer Diabetes

Khwaja Salahuddin Siddiqi, Azamal Husen, Sayed Sartaj Sohrab, Mensur Osman Yassin
Nanomaterials (NMs) are receiving remarkable attention due to their unique properties and structure. They vary from atoms and molecules along with those of bulk materials. They can be engineered to act as drug delivery vehicles to cross blood-brain barriers (BBBs) and utilized with better efficacy and safety to deliver specific molecules into targeted cells as compared to conventional system for neurological disorders. Depending on their properties, various metal chelators, gold nanoparticles (NPs), micelles, quantum dots, polymeric NPs, liposomes, solid lipid NPs, microparticles, carbon nanotubes, and fullerenes have been utilized for various purposes including the improvement of drug delivery system, treatment response assessment, diagnosis at early stage, and management of neurological disorder by using neuro-engineering...
August 10, 2018: Nanoscale Research Letters
Jinping Cheng, Nils Korte, Ross Nortley, Huma Sethi, Yamei Tang, David Attwell
Many central nervous system diseases currently lack effective treatment and are often associated with defects in microvascular function, including a failure to match the energy supplied by the blood to the energy used on neuronal computation, or a breakdown of the blood-brain barrier. Pericytes, an under-studied cell type located on capillaries, are of crucial importance in regulating diverse microvascular functions, such as angiogenesis, the blood-brain barrier, capillary blood flow and the movement of immune cells into the brain...
August 10, 2018: Acta Neuropathologica
Fiona H McLean, Christine Grant, Amanda C Morris, Graham W Horgan, Alex J Polanski, Kevin Allan, Fiona M Campbell, Rosamund F Langston, Lynda M Williams
Alzheimer's disease is a leading cause of morbidity and mortality with no cure and only limited treatment available. Obesity and type 2 diabetes are positively associated with the development of premature cognitive decline and Alzheimer's disease, linking diet with these conditions. Here we demonstrate that in mice episodic memory, together with spatial and contextual associative memory, is compromised after only one day of high-fat diet. However, object memory remains intact. This shows not only a more rapid effect than previously reported but also that more complex memories are at higher risk of being compromised by a high-fat diet...
August 10, 2018: Scientific Reports
Marzia Bianchi, Melania Manco
Prolyl isomerases (Peptidylprolyl isomerase, PPIases) are enzymes that catalyze the isomerization between the cis / trans Pro conformations. Three subclasses belong to the class: FKBP (FK506 binding protein family), Cyclophilin and Parvulin family (Pin1 and Par14). Among Prolyl isomerases, Pin1 presents as distinctive feature, the ability of binding to the motif pSer/pThr-Pro that is phosphorylated by kinases. Modulation of Pin1 is implicated in cellular processes such as mitosis, differentiation and metabolism: The enzyme is dysregulated in many diverse pathological conditions, i...
August 8, 2018: International Journal of Molecular Sciences
Anna Czarna, Jinhua Wang, Diana Zelencova, Yao Liu, Xianming Deng, Hwan Geun Choi, Tinghu Zhang, Wenjun Zhou, Jae Won Chang, Hanne Kildalsen, Ole-Morten Seternes, Nathanael S Gray, Richard Alan Engh, Ulli Rothweiler
DYRK1A is one of five members of the Dual-specificity tyrosine (Y) phosphorylation-Regulated Kinase (DYRK) family. The DYRK1A gene is located in the Down syndrome critical region and regulates cellular processes related to proliferation and differentiation of neuronal progenitor cells during early development. This has focused research on to its role in neuronal degenerative diseases, including Alzheimer's and Down syndrome; recent studies have also shown a possible role of DYRK1A in diabetes. Here we report a variety of scaffolds not generally known for DYRK1A inhibition, demonstrating their effects in in vitro assays and also in cell cultures...
August 10, 2018: Journal of Medicinal Chemistry
Yuhui Wang, Jinyang Shen, Xiaolin Yang, Ye Jin, Zhonglin Yang, Rufeng Wang, Fuming Zhang, Robert J Linhardt
BACKGROUND: Glucocorticoid hormones are implicated in the pathogenesis of Alzheimer's disease (AD) and other diseases including diabetes, hyperlipidemia, and osteoporosis. Akebia saponin D (ASD) possesses numerous pharmacological activities, including as an anti-AD, anti-hyperlipidemia, anti-diabetes, and anti-osteoporosis agent. The anti-AD effect of ASD is possibly through its regulation of glucocorticoid levels. PURPOSE: The present study was undertaken to investigate the neuroprotective effects of ASD on Aβ25-35 -induced cognitive deficits and to elucidate its underlying mechanism of action...
August 6, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Nandkishor K Mule, Jitendra Narain Singh
Diabetes and neurodegenerative diseases (ND) are progressive morbidities and in themselves represent a major public health burden. A growing body of evidence points towards the comorbidity of diabetes and NDs with a possible exacerbation of latter by former. Considering the high prevalence of both morbidities in aging world population, even a modest impact of diabetes on NDs could lead to significant public health implications. Several hypotheses and mechanistic evidence were proposed linking altered glucose metabolism to the risk of progressive dementia...
August 8, 2018: CNS & Neurological Disorders Drug Targets
Sibo Wang, Zhihui Ma, Yongjun Zhang, Yankui Ding, Zhong Chen, Liansheng Wang
BACKGROUND: Adaptor-related protein complex 2 alpha 2 subunit (AP2A2) gene encodes a protein-a subunit of the AP-2 adaptor protein complex. Evidence has revealed that benzodiazepine receptor-associated protein 1 (BZRAP1) is abundant in the hippocampus with potential effects on brain diseases. Recently, an epidemiological study reported that two variants (rs7396366 and rs2526378) closest to the AP2A2 and BZRAP1 genes are associated with higher plasma lipids and Alzheimer's disease. Whether the two single nucleotide polymorphisms (SNPs) are actually relevant to coronary artery disease (CAD) and CAD severity remains elusive...
August 7, 2018: BMC Cardiovascular Disorders
Ana C Silveira, Jane Pires Dias, Vanessa M Santos, Pedro Fontes Oliveira, Marco G Alves, Luis Rato, Branca M Silva
Diabetes Mellitus (DM) and Alzheimer's disease (AD) are two prevalent diseases in modern societies, which are caused mainly by current lifestyle, aging and genetic alterations. It has already been demonstrated that these two diseases are associated since individuals suffering from DM are prone to develop AD. Conversely, it is also known that individuals with AD are more susceptible to DM, namely type 2 diabetes (T2DM). Therefore, these two pathologies, although completely different in terms of symptomatology, end up sharing several mechanisms at the molecular level, being the most obvious the increase of oxidative stress and inflammation...
August 3, 2018: Current Neuropharmacology
Gokalp Ozmen Guler, Gokhan Zengin, Firat Karadag, Adriano Mollica, Carene Marie Nancy Picot, Mohamad Fawzi Mahomoodally
Onobrychis argyrea Boiss. subsp. Isaurica (Fabaceae), endemic to the eastern Mediterranean region, is a poorly studied medicinal plant. This study sets out to investigate into antioxidant and inhibitory activities of O. argyrea extracts (ethyl acetate, methanol, and water) against key enzymes linked to diabetes (α-amylase, α-glucosidase), Alzheimer's disease (acetylcholinesterase, butyrylcholinesterase), and skin hyperpigmentation (tyrosinase). Phytochemical composition was determined by HPLC-DAD and in silico approach used to provide additional insight of the possible interaction of the identified phenolic compounds with the studied enzymes...
July 29, 2018: Computational Biology and Chemistry
Shirin Elhaik Goldman, David Goez, David Last, Sharone Naor, Sigal Liraz Zaltsman, Inbal Sharvit-Ginon, Dana Atrakchi-Baranes, Chen Shemesh, Rachel Twitto-Greenberg, Shoval Tsach, Roni Lotan, Alicia Leikin-Frenkel, Aviv Shish, Yael Mardor, Michal Schnaider Beeri, Itzik Cooper
Type 2 diabetes (T2D) is associated with increased risk of Alzheimer's disease (AD). There is evidence for impaired blood-brain barrier (BBB) in both diseases, but its role in the interplay between them is not clear. Here, we investigated the effects of high-fat diet (HFD), a model for T2D, on the Tg2576 mouse model of AD, in regard to BBB function. We showed that HFD mice had higher weight, more insulin resistance, and higher serum HDL cholesterol levels, primarily in Tg2576 mice, which also had higher brain lipids content...
August 6, 2018: Aging Cell
Dong Cui, Shunai Qi, Guanghua Gu, Xiaoli Li, Zhaohui Li, Lei Wang, Shimin Yin
Type 2 diabetes mellitus (T2DM) increases the risk of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease(AD). aMCI is the transitory stage from normal cognition to AD, which seriously impacts the quality of human life, especially for old people. Electroencephalography (EEG) coherence can assess the functional connectivity between different brain regions, which is an effective way to research the pathogenesis of aMCI and distinguish aMCI patients from normal cognitive subjects. In this paper, we propose a new EEG coherence approach named magnitude squared coherence based on weighted canonical correlation analysis (WCCA-MSC) which improves the accuracy in coherence estimation by the means of weighting...
August 2, 2018: IEEE Transactions on Neural Systems and Rehabilitation Engineering
Antonio C Bianco, Brian S Kim
PURPOSE OF REVIEW: To assess new findings and clinical implications of deiodinase gene polymorphism. Deiodinases are enzymes that can activate or inactivate thyroid hormone molecules. Whereas the types 1 and 2 deiodinase (D1 and D2) activate thyroxine (T4) to 3,5,3'-triiodothyronine (T3) via deiodination of T4's outer ring, D1 and D3 inactivate both T4 and T3 and terminate thyroid hormone action via deiodination of T4's inner molecular ring. A number of polymorphisms have been identified in the three deiodinase genes; the most investigated and likely to have clinical relevance is the Thr92 substitution for Ala substitution in DIO2 (Thr92Ala-DIO2)...
July 30, 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
Fan Hong, Pengfei Xu, Yonggong Zhai
Peroxisome proliferator-activated receptors (PPARs) are a well-known pharmacological target for the treatment of multiple diseases, including diabetes mellitus, dyslipidemia, cardiovascular diseases and even primary biliary cholangitis, gout, cancer, Alzheimer's disease and ulcerative colitis. The three PPAR isoforms (α, β/δ and γ) have emerged as integrators of glucose and lipid metabolic signaling networks. Typically, PPARα is activated by fibrates, which are commonly used therapeutic agents in the treatment of dyslipidemia...
July 27, 2018: International Journal of Molecular Sciences
Fernando Gomez-Pinilla, Xia Yang
The surge in meals high in calories has prompted an epidemic of metabolic disorders around the world such that the elevated incidence of obese and diabetic individuals is alarming. New research indicates that metabolic disorders pose a risk for neurological and psychiatric conditions including stroke, Alzheimer's disease, Huntington's disease, and depression, all of which have a metabolic component. These relationships are rooted to a dysfunctional interaction between molecular processes that regulate energy metabolism and synaptic plasticity...
July 27, 2018: Progress in Neurobiology
Tiantian Tang, Tao Gong, Wei Jiang, Rongbin Zhou
The NLRP3 inflammasome is an intracellular multimeric protein complex which plays an important role in the pathogenesis of various human inflammatory diseases, such as diabetes, Alzheimer's disease and atherosclerosis. Recently, various G protein-coupled receptors (GPCRs) have been reported to be involved in the activation and regulation of the NLRP3 inflammasome by sensing multiple ions, metabolites, and neurotransmitters, suggesting GPCR signaling is an important regulator for NLRP3 inflammasome. Here, we will review how various GPCRs promote or inhibit NLRP3 inflammasome activation and discuss the implications of GPCRs as drug targets for the therapy of NLRP3-driven diseases...
July 24, 2018: Trends in Pharmacological Sciences
Uilson Pereira Dos Santos, Georgina S Tolentino, Jorge Sá Morais, Kely de Picoli Souza, Leticia M Estevinho, Edson Lucas Dos Santos
Hancornia speciosa Gomes is a fruit tree, commonly known as the mangaba tree, which is widespread throughout Brazil. The leaves of this plant are used in traditional medicine for medicinal purposes. Thus, the objective of this study was to perform a physicochemical characterization, identify the lipophilic antioxidants and fatty acids, and determine the microbiological quality and safety of H. speciosa leaves. In addition, the antioxidant, antimutagenic, and inhibitory activities of the ethanolic extract of H...
2018: Oxidative Medicine and Cellular Longevity
Zarish Noreen, Jessica DeJesus, Attya Bhatti, Christopher A Loffredo, Peter John, Jahangir S Khan, Gail Nunlee-Bland, Somiranjan Ghosh
The epidemic of type 2 diabetes mellitus (T2DM) and the possibility of it contributing to the risk of Alzheimer's disease (AD) have become important health concerns worldwide and in Pakistan, where the co-occurrence of T2DM and AD is becoming more frequent. To gain insights on this phenomenon, a cross-sectional study was initiated. We recruited and interviewed 820 research participants from four cities in Pakistan: 250 controls, 450 T2DM, 100 AD, and 20 with both diseases. Significant differences between groups were observed for age ( p < 0...
July 26, 2018: International Journal of Environmental Research and Public Health
Nurul 'Ain Arshad, Teoh Seong Lin, Mohamad Fairuz Yahaya
Metabolic syndrome (MetS) is an interconnected group of physiological, biochemical, clinical and metabolic factors that directly increases the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) and mortality. Rising evidence suggests that MetS plays a significant role in the progression of Alzheimer's disease and other neurodegenerative diseases. Nonetheless, the factors linking this association has not yet been elucidated. As we are facing an increasing incidence of obesity and T2DM in all stages of life, understanding the association of MetS and neurodegenerative diseases is crucial to lessen the burden of the disease...
July 24, 2018: CNS & Neurological Disorders Drug Targets
Ji Yeon Chung, Hyung-Seok Kim, Juhyun Song
Alzheimer's disease (AD) is characterized by an excessive accumulation of toxic amyloid beta (Aβ) plaques and memory dysfunction. The onset of AD is influenced by age, genetic background, and impaired glucose metabolism in the brain. Several studies have demonstrated that diabetes involving insulin resistance and glucose tolerance could lead to AD, ultimately resulting in cognitive dysfunction. Even though the relationship between diabetes and AD was indicated by significant evidences, the critical mechanisms and metabolic alterations in diabetes induced AD are not clear until now...
July 24, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
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