Highlighted Article – Default Mode Network Connectivity and Related White Matter Disruption in Type 2 Diabetes Mellitus Patients Concurrent with Amnestic Mild Cognitive Impairment – Current Alzheimer Research

CAR-Articles_14-Zhanjun Zhang

To access this article, please visit: http://www.eurekaselect.com/151651

Highlighted Article – A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in In Vitro SH-SY5Y Cells – Current Alzheimer Research

car-14-Sourav Kumar

To access this article, please visit: http://www.eurekaselect.com/154200

 

Testimonial by Rosanna Squitt!

Rosanna Squitt

Contributed Article: “Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer’s Disease: A Neuroimaging Study

 

 

World Mental Health Day 2017!

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World Mental Health Day is observed on 10 October every year, with the overall objective of raising awareness of mental health issues around the world and mobilizing efforts in support of mental health.

Bentham Science Publishers has various research journals dedicated to the mental health research. The most significant ones are:

CURRENT NEUROPHARMACOLOGY

CURRENT ALZHEIMER RESEARCH

World Alzheimer’s Day 2017!

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World Alzheimer’s Day is observed annually on 21 September each year to raise awareness and challenge the stigma that surrounds dementia. Alzheimer’s disease is the most common form of dementia, a group of disorders that impairs mental functioning.

Bentham Science Publishers is in the forefront in creating awareness about this through the research in the journal:

Current Alzheimer Research

Open Access Article – iTRAQ-based Proteomic Analysis of APPSw,Ind Mice Provides Insights into the Early Changes in Alzheimer’s Disease – Current Alzheimer Research

Journal: Current Alzheimer Research

Author(s): Nan Li, Pinghong Hu, Tiantian Xu, Huan Chen, Xiaoying Chen, Jianwen Hu, Xifei Yang, Lei Shi, Jian-hong Luo, Junyu Xu.

Abstract:

Background: Several proteins have been identified as potential diagnostic biomarkers in imaging, genetic, or proteomic studies in Alzheimer disease (AD) patients and mouse models. However, biomarkers for presymptom diagnosis of AD are still under investigation, as are the presymptom molecular changes in AD pathogenesis.

Objective: In this study, we aim to analyzed the early proteomic changes in APPSw,Ind mice and to conduct further functional studies on interesting proteins.

Methods: We used the isobaric tags for relative and absolute quantitation (iTRAQ) approach combined with mass spectrometry to examine the early proteomic changes in hippocampi of APPSw,Ind mice. Quantitative reverse transcription polymerase chain reaction (RT-PCR) and immuno-blotting were performed for further validation. Finally, the functions of interesting proteins β-spectrin and Rab3a in APP trafficking and processing were tested by shRNA knockdown, in N2A cells stably expressing β-amyloid precursor protein (APP).
Results: The iTRAQ and RT-PCR results revealed the detailed molecular changes in oxidative stress, myelination, astrocyte activation, mTOR signaling and Rab3-dependent APP trafficking in the early stage of AD progression. Knock down of β -spectrin and Rab3a finally led to increased APP fragment production, indicating key roles of β-spectrin and Rab3a in regulating APP processing.
Conclusion: Our study provides the first insights into the proteomic changes that occur in the hippocampus in the early stages of the AD mouse model. In addition to improving the understanding of molecular alterations and functional cascades involved in early AD pathogenesis, our findings raise the possibility of developing potential biomarkers and therapeutic targets for early AD.

Press Release for EurekAlert! Inhibition of tau protein aggregation by rhodanine-based compounds

This research article by Dr. Eckhard Mandelkow et al has been published in Current Alzheimer Research, Volume 14, Issue 7, 2017

 

The design of tailored peptide-polymer conjugates as drug-specific formulation additives offers access to next generation precision additives that can render problematic small organic drugs water-soluble and improve bioavailability. The method can be applied to a large spectrum of entities of fluorescent or non-fluorescent drugs. Herein we report the solubilization of two poorly water-soluble, potential anti-Alzheimer disease (AD) drugs based on the rhodanine core. The compounds showed inhibitory activity to prevent the aggregation of Tau proteins into paired helical filaments (PHFs) and neurofibrillary tangles (NFTs), both of which are associated with AD pathogenesis.

Using a fluorescence microscopy-based screening procedure, peptide sequences with high drug binding capacity are identified from large peptide libraries. The synthesis of corresponding peptide-poly(ethylene glycol) (peptide-PEG) conjugates leads to precision formulation additives for the potential anti-AD drugs. Whereas the PEG-blocks of the conjugates provide water solubility and drug shielding, the drug specific hosting is dominated by the peptide-segments, binding the drug in a non-covalent manner and thus bypassing the requirements of additional drug approval procedures.

Application in several bioassays of inhibition of Tau protein aggregation indicated that the formulation additives do not reduce drug efficacy and activity. The drug formulations showed a reduction of the fibril formation of the tested Tau construct comparable to the drug alone dissolved in DMSO. Thus, drug release from the conjugates is feasible. The activities of the compound-complexes in in vitro experiments on Tau4RDΔK280-expressing N2a cells were significantly enhanced, resulting in improved cell viability and reduced apoptosis, which correlates with a lower ratio of insoluble to soluble Tau aggregates.

The precision formulation additives offer opportunities for early stage drug structure or lead compound testing in DMSO free systems. This is important as DMSO is currently believed to affect relevant protein functions and might influence cell studies.

For more information, please visit http://www.eurekaselect.com/149699/article

Wishing A Very Happy Birthday to Prof. Debomoy K. Lahiri!

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Prof. Debomoy K. Lahiri

EDITOR-IN-CHIEF: Current Alzheimer Research & Current Aging Science

Department of Psychiatry Indiana University School of Medicine
Indianapolis, IN
USA

New Issue :: Current Alzheimer Research 14, Issue 5

Current Alzheimer Research publishes peer-reviewed frontier review, research, drug clinical trial studies and letter articles on all areas of Alzheimer’s disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer’s disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer’s disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer’s disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer’s disease. Current Alzheimer Research provides a comprehensive ‘bird’s-eye view’ of the current state of Alzheimer’s research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

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Articles from the journal Current Alzheimer Research 14, Issue 5:

    For details on the articles, please visit this link :: http://bit.ly/2suX713

 

Editor’s Choice – “Beyond Acetylcholinesterase Inhibitors: Novel Cholinergic Treatments for Alzheimer’s Disease”

Journal: Current Alzheimer’s Research

Author(s):  Asante R. Kamkwalala, Paul A. Newhouse

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Abstract:

The major components of the cholinergic receptor system of the human brain include projections from the basal forebrain nuclei, and utilize the two types of receptors that they synapse on, nicotinic and muscarinic acetylcholine receptors. With the widespread cortical and subcortical projections of the basal forebrain, activity of these two receptor systems provide modulation of neurotransmitter activity underlying normal cognitive processes, such as attention, episodic memory, and working memory. Alzheimer’s disease (AD) targets and damages cholinergic neurons in the basal forebrain, and as these projections are lost, cognitive performance progressively declines. Currently, the most widely prescribed treatment for AD is acetylcholinesterase inhibitor medications, which work by partially blocking the degradation of acetylcholine in the synapse and enabling more of the neurotransmitter to reach and activate cholinergic receptors. However since these medications have limited effectiveness, alternate treatments that focus on augmenting the activity of the receptors themselves, independent of acetylcholinesterase inhibition, are being explored. This review will discuss: 1) the role of the cholinergic system in modulating cognition, 2) novel cholinergic treatment strategies for AD-related cognitive decline, in particular treatments intended to increase cholinergic system activity by selectively targeting muscarinic and nicotinic acetylcholinergic receptors to improve cognitive performance, 3) risks, and additional considerations for cholinergic cognitive treatments for AD.

Read more here: http://www.eurekaselect.com/145925