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Molecular Insight into Alzheimer’s Disease

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: 20 July 2025 | Viewed by 2928

Special Issue Editors


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Guest Editor
Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Inserm U1256, Campus Brabois, University of Lorraine, 54500 Vandœuvre-lès-Nancy, France
Interests: brain aging; Alzheimer’s disease; neurodegenerative diseases; neuronal membranes; lipids; nutrition; membrane protein interactions; endocytosis; vesicular trafficking

E-Mail Website
Guest Editor
Nutrition-Génétique et Exposition aux Risques Environnementaux (N-GERE), Inserm U1256, Campus Brabois, University of Lorraine, 54500 Vandœuvre-lès-Nancy, France
Interests: brain aging; Alzheimer’s disease; neurodegenerative diseases; neuronal membranes; lipids; nutrition; membrane protein interactions; endocytosis; vesicular trafficking; biomarkers
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Special Issue Information

Dear Colleagues,

Alzheimer’s disease is the most common form of dementia in the world. Identified as a neurodegenerative disease that mainly affects the elderly, it profoundly changes the functioning of the brain, thereby affecting cognitive functions such as memory to the point of threatening the autonomy of patients and altering their quality of life as well as that of those around them. These devastating consequences clearly pose a priority societal and public health issue.

The very active multidisciplinary research that began decades ago continues to explore many very diverse avenues, with the aim of contributing to improving diagnosis as well as the treatment and care of patients. Thousands of researchers around the world are still working today to better understand the causes of the disease, as well as the mechanisms involved in its onset and progression, particularly in order to identify preventive or curative therapeutic solutions.

The aim of this Special Issue is to bring together some of the most recent and convincing advances in the cellular and molecular mechanisms associated with Alzheimer’s disease, without bias or a priori on the hypotheses developed. This Special Issue will accept original studies as well as reviews.

Dr. Thierry Oster
Dr. Catherine Malaplate
Guest Editors

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Keywords

  • Alzheimer’s disease
  • cellular and molecular mechanisms
  • neuronal membranes, endocytosis, and vesicular trafficking
  • molecular crosstalk between neurons and glial cells
  • protein interaction with lipids or other proteins
  • biomarkers and diagnosis
  • epidemiology, risk factors, and prevention
  • therapeutic visions

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Published Papers (2 papers)

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Research

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18 pages, 3477 KiB  
Article
Diverse Interactions of Sterols with Amyloid Precursor Protein Transmembrane Domain Can Shift Distribution Between Alternative Amyloid-β Production Cascades in Manner Dependent on Local Lipid Environment
by Pavel E. Volynsky, Anatoly S. Urban, Konstantin V. Pavlov, Yaroslav V. Bershatsky, Olga V. Bocharova, Anastasia K. Kryuchkova, Veronika V. Zlobina, Alina A. Gavrilenkova, Sofya M. Dolotova, Anna V. Kamynina, Olga T. Zangieva, Amir Taldaev, Oleg V. Batishchev, Ivan S. Okhrimenko, Tatiana V. Rakitina, Roman G. Efremov and Eduard V. Bocharov
Int. J. Mol. Sci. 2025, 26(2), 553; https://doi.org/10.3390/ijms26020553 - 10 Jan 2025
Cited by 1 | Viewed by 986
Abstract
Alzheimer’s disease (AD) pathogenesis is correlated with the membrane content of various lipid species, including cholesterol, whose interactions with amyloid precursor protein (APP) have been extensively explored. Amyloid-β peptides triggering AD are products of APP cleavage by secretases, which differ depending on the [...] Read more.
Alzheimer’s disease (AD) pathogenesis is correlated with the membrane content of various lipid species, including cholesterol, whose interactions with amyloid precursor protein (APP) have been extensively explored. Amyloid-β peptides triggering AD are products of APP cleavage by secretases, which differ depending on the APP and secretase location relative to ordered or disordered membrane microdomains. We used high-resolution NMR to probe the interactions of the cholesterol analog with APP transmembrane domain in two membrane-mimicking systems resembling ordered or perturbed lipid environments (bicelles/micelles). In bicelles, spin-labeled sterol interacted with the peptide near the amphiphilic juxtamembrane region and N-terminal part of APP transmembrane helix, as described earlier for cholesterol. Upon transition into micellar environment, another interaction site appeared where sterol polar head was buried in the hydrophobic core near the hinge region. In MD simulations, sterol moved between three interaction sites, sliding along the polar groove formed by glycine residues composing the dimerization interfaces and flexible hinge of the APP transmembrane domain. Because the lipid environment modulates interactions, the role of lipids in the AD pathogenesis is defined by the state of the entire lipid subsystem rather than the effects of individual lipid species. Cholesterol can interplay with other lipids (polyunsaturated, gangliosides, etc.), determining the outcome of amyloid-β production cascades. Full article
(This article belongs to the Special Issue Molecular Insight into Alzheimer’s Disease)
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Review

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12 pages, 2159 KiB  
Review
Molecular Roles of NADPH Oxidase-Mediated Oxidative Stress in Alzheimer’s Disease: Isoform-Specific Contributions
by Junhyung Kim and Jong-Seok Moon
Int. J. Mol. Sci. 2024, 25(22), 12299; https://doi.org/10.3390/ijms252212299 - 15 Nov 2024
Cited by 2 | Viewed by 1512
Abstract
Oxidative stress is linked to the pathogenesis of Alzheimer’s disease (AD), a neurodegenerative disorder marked by memory impairment and cognitive decline. AD is characterized by the accumulation of amyloid-beta (Aβ) plaques and the formation of neurofibrillary tangles (NFTs) of hyperphosphorylated tau. AD is [...] Read more.
Oxidative stress is linked to the pathogenesis of Alzheimer’s disease (AD), a neurodegenerative disorder marked by memory impairment and cognitive decline. AD is characterized by the accumulation of amyloid-beta (Aβ) plaques and the formation of neurofibrillary tangles (NFTs) of hyperphosphorylated tau. AD is associated with an imbalance in redox states and excessive reactive oxygen species (ROS). Recent studies report that NADPH oxidase (NOX) enzymes are significant contributors to ROS generation in neurodegenerative diseases, including AD. NOX-derived ROS aggravates oxidative stress and neuroinflammation during AD. In this review, we provide the potential role of all NOX isoforms in AD pathogenesis and their respective structural involvement in AD progression, highlighting NOX enzymes as a strategic therapeutic target. A comprehensive understanding of NOX isoforms and their inhibitors could provide valuable insights into AD pathology and aid in the development of targeted treatments for AD. Full article
(This article belongs to the Special Issue Molecular Insight into Alzheimer’s Disease)
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