ijms-logo

Journal Browser

Journal Browser

Special Issue "Alzheimer’s Disease and Other Dementias-Novel Therapeutic Approaches"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 25 March 2020.

Special Issue Editors

Prof. Hanna Rosenmann
E-Mail Website
Guest Editor
Hadassah University Medical Centre, Department of Neurology, Jerusalem, Israel
Tel. 97226776954
Interests: Alzheimer's disease; tauopathy; neurodegeneration; animal models
Prof. Dan Frenkel
E-Mail Website
Guest Editor
Department of Neurobiology, Faculty of Life Sciences, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
Interests: Neuroinflammation; astrocyte; microglia; Alzheimer’s disease; animal model

Special Issue Information

Dear Colleagues,

Although Alzheimer's disease (AD) and other dementias are being intensively investigated, there is not yet a drug that efficiently interferes with disease pathogenesis. Most cases of AD are sporadic and less than 5%, among them carrying mutations that affect beta amyloid, are early‐onset familial AD that occur before the age of 65 years. Unfortunately, thus far, most of the newly developed drugs for AD treatment have failed in clinical trials. There is an urgent need for new therapies for treating dementias, particularly AD. Otherwise, this disease will continue to attack 5% of people aged over 65 and more than 40% of those aged over 85. Genetic risk factors, such as the presence of ApoE4 or mutations in inflammatory markers, such as TREM2, have been shown to affect disease development and progress. However, preventive approaches, such as maintaining good health (e.g., reducing cardiovascular and metabolic risk factors, enhancing physical and mental activities), seem to have a major impact on reducing disease incidence and delaying its onset. Many research approaches may be suitable for combating dementias, such as identifying disease-causing compounds (toxins), finding new targets, developing new drugs (mono/multi-target) by drug screening or by drug design, cell or organelle therapy, and device development, as well as other creative and innovative unconventional approaches.

This Special Issue will be dedicated to gathering novel therapeutic approaches to treat Alzheimer's disease and other dementias. We welcome submissions, including original papers and reviews, on these essential topics.

Prof. Hanna Rosenmann
Prof. Dan Frenkel
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Dementia
  • Prevention of dementia
  • Treatment of dementia
  • Amyloid
  • Tangles
  • Tauopathies
  • Mild cognitive impairment
  • Neurodegenerative pathways
  • Toxic elements inducing dementia
  • Drug screening
  • Drug design
  • Cell or organelle therapy
  • Device development
  • Neurodegeneration
  • Neuroinflammation

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Open AccessArticle
Central and Peripheral Mechanisms in ApoE4-Driven Diabetic Pathology
Int. J. Mol. Sci. 2020, 21(4), 1289; https://doi.org/10.3390/ijms21041289 (registering DOI) - 14 Feb 2020
Abstract
Apolipoprotein E (APOE) ε4 gene allele and type 2 diabetes mellitus (T2DM) are prime risk factors for Alzheimer’s disease (AD). Despite evidence linking T2DM and apoE4, the mechanism underlying their interaction is yet to be determined. In the present study, we [...] Read more.
Apolipoprotein E (APOE) ε4 gene allele and type 2 diabetes mellitus (T2DM) are prime risk factors for Alzheimer’s disease (AD). Despite evidence linking T2DM and apoE4, the mechanism underlying their interaction is yet to be determined. In the present study, we employed a model of APOE-targeted replacement mice and high-fat diet (HFD)-induced insulin resistance to investigate diabetic mechanisms associated with apoE4 pathology and the extent to which they are driven by peripheral and central processes. Results obtained revealed an intriguing pattern, in which under basal conditions, apoE4 mice display impaired glucose and insulin tolerance and decreased insulin secretion, as well as cognitive and sensorimotor characteristics relative to apoE3 mice, while the HFD impairs apoE3 mice without significantly affecting apoE4 mice. Measurements of weight and fasting blood glucose levels increased in a time-dependent manner following the HFD, though no effect of genotype was observed. Interestingly, sciatic electrophysiological and skin intra-epidermal nerve fiber density (IENFD) peripheral measurements were not affected by the APOE genotype or HFD, suggesting that the observed sensorimotor and cognitive phenotypes are related to central nervous system processes. Indeed, measurements of hippocampal insulin receptor and glycogen synthase kinase-3β (GSK-3β) activation revealed a pattern similar to that obtained in the behavioral measurements while Akt activation presented a dominant effect of diet. HFD manipulation induced genotype-independent hyperlipidation of apoE, and reduced levels of brain apoE in apoE3 mice, rendering them similar to apoE4 mice, whose brain apoE levels were not affected by the diet. No such effect was observed in the peripheral plasma levels of apoE, suggesting that the pathological effects of apoE4 under the control diet and apoE3 under HFD conditions are related to the decreased levels of brain apoE. Taken together, our data suggests that diabetic mechanisms play an important role in mediating the pathological effects of apoE4 and that consequently, diabetic-related therapy may be useful in treating apoE4 pathology in AD. Full article
Show Figures

Figure 1

Open AccessArticle
Caspase-6 Knockout in the 5xFAD Model of Alzheimer’s Disease Reveals Favorable Outcome on Memory and Neurological Hallmarks
Int. J. Mol. Sci. 2020, 21(3), 1144; https://doi.org/10.3390/ijms21031144 - 09 Feb 2020
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and is the most common form of dementia in the elderly. Caspases, a family of cysteine proteases, are major mediators of apoptosis and inflammation. Caspase-6 is considered to be an up-stream modulator of AD pathogenesis [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and is the most common form of dementia in the elderly. Caspases, a family of cysteine proteases, are major mediators of apoptosis and inflammation. Caspase-6 is considered to be an up-stream modulator of AD pathogenesis as active caspase-6 is abundant in neuropil threads, neuritic plaques, and neurofibrillary tangles of AD brains. In order to further elucidate the role of caspase-6 activity in the pathogenesis of AD, we produced a double transgenic mouse model, combining the 5xFAD mouse model of AD with caspase-6 knock out (C6-KO) mice. Behavioral examinations of 5xFAD/C6-KO double transgenic mice showed improved performance in spatial learning, memory, and anxiety/risk assessment behavior, as compared to 5xFAD mice. Hippocampal mRNA expression analyses showed significantly reduced levels of inflammatory mediator TNF-α, while the anti-inflammatory cytokine IL-10 was increased in 5xFAD/C6-KO mice. A significant reduction in amyloid-β plaques could be observed and immunohistochemistry analyses showed reduced levels of activated microglia and astrocytes in 5xFAD/C6-KO, compared to 5xFAD mice. Together, these results indicate a substantial role for caspase-6 in the pathology of the 5xFAD model of AD and suggest further validation of caspase-6 as a potential therapeutic target for AD. Full article
Show Figures

Figure 1

Open AccessArticle
The Clustering of mApoE Anti-Amyloidogenic Peptide on Nanoparticle Surface Does Not Alter Its Performance in Controlling Beta-Amyloid Aggregation
Int. J. Mol. Sci. 2020, 21(3), 1066; https://doi.org/10.3390/ijms21031066 - 05 Feb 2020
Abstract
The deposition of amyloid-β (Aβ) plaques in the brain is a significant pathological signature of Alzheimer’s disease, correlating with synaptic dysfunction and neurodegeneration. Several compounds, peptides, or drugs have been designed to redirect or stop Aβ aggregation. Among them, the trideca-peptide CWG-LRKLRKRLLR (mApoE), [...] Read more.
The deposition of amyloid-β (Aβ) plaques in the brain is a significant pathological signature of Alzheimer’s disease, correlating with synaptic dysfunction and neurodegeneration. Several compounds, peptides, or drugs have been designed to redirect or stop Aβ aggregation. Among them, the trideca-peptide CWG-LRKLRKRLLR (mApoE), which is derived from the receptor binding sequence of apolipoprotein E, is effectively able to inhibit Aβ aggregation and to promote fibril disaggregation. Taking advantage of Atomic Force Microscopy (AFM) imaging and fluorescence techniques, we investigate if the clustering of mApoE on gold nanoparticles (AuNP) surface may affect its performance in controlling Aβ aggregation/disaggregation processes. The results showed that the ability of free mApoE to destroy preformed Aβ fibrils or to hinder the Aβ aggregation process is preserved after its clustering on AuNP. This allows the possibility to design multifunctional drug delivery systems with clustering of anti-amyloidogenic molecules on any NP surface without affecting their performance in controlling Aβ aggregation processes. Full article
Show Figures

Figure 1

Back to TopTop