Alzheimer\u27s disease (AD) and other dementias are neurodegenerative disorders characterized by a progressive decline in cognition and independence from activities of daily living. Dementia is multifactorial with numerous risk factors including age, genes, molecules, lifestyle, and environmental contributions to disease onset and progression. In recent years, an emerging focus on neurotoxins has added a new layer of complexity to our understanding of dementia. This editorial aims to discuss recent updates regarding the role of neurotoxins in the pathogenesis of dementia

Fernando, Binosha

Hascup, Kevin N.

Henriques, Alexandre

Poindron, Philippe L. L.

English

Research Online @ ECU

Edith Cowan University Research Online Research outputs 2022 to 2026 1-1-2024 Editorial: Neurotoxins in Alzheimer's disease and other dementias Alexandre Henriques Philippe L. L. Poindron Binosha Fernando Edith Cowan University Kevin N. Hascup Follow this and additional works at: https://ro.ecu.edu.au/ecuworks2022-2026  Part of the Diseases Commons, and the Neurosciences Commons 10.3389/fnagi.2024.1363466 Henriques, A., Poindron, P. L. L., Fernando, B., & Hascup, K. N. (2024). Editorial: Neurotoxins in Alzheimer's disease and other dementias [Editorial]. Frontiers in Aging Neuroscience, 16, article 1363466. https://doi.org/10.3389/fnagi.2024.1363466 This Editorial is posted at Research Online. https://ro.ecu.edu.au/ecuworks2022-2026/3615 TYPE EditorialPUBLISHED 11 January 2024DOI 10.3389/fnagi.2024.1363466OPEN ACCESSEDITED AND REVIEWED BYAgustin Ibanez,Latin American Brain Health Institute(BrainLat), Chile*CORRESPONDENCEKevin N. Hascupkhascup49@siumed.eduRECEIVED 30 December 2023ACCEPTED 03 January 2024PUBLISHED 11 January 2024CITATIONHenriques A, Poindron PLL, Fernando B andHascup KN (2024) Editorial: Neurotoxins inAlzheimer’s disease and other dementias.Front. Aging Neurosci. 16:1363466.doi: 10.3389/fnagi.2024.1363466COPYRIGHT© 2024 Henriques, Poindron, Fernando andHascup. This is an open-access articledistributed under the terms of the CreativeCommons Attribution License (CC BY). Theuse, distribution or reproduction in otherforums is permitted, provided the originalauthor(s) and the copyright owner(s) arecredited and that the original publication inthis journal is cited, in accordance withaccepted academic practice. No use,distribution or reproduction is permittedwhich does not comply with these terms.Editorial: Neurotoxins inAlzheimer’s disease and otherdementiasAlexandre Henriques1, Philippe Léon Louis Poindron1,Binosha Fernando2 and Kevin N. Hascup3*1Neuro-Sys, Gardanne, France, 2Centre of Excellence for Alzheimer’s Disease Research and CareSchool of Medical and Health Sciences, Edith Cowan University, SNRI, Nedlands, WA, Australia,3Department of Neurology, Pharmacology, and Medical Microbiology, Immunology and Cell Biology,Center for Alzheimer’s Research and Treatment, Southern Illinois University School of Medicine,Springfield, IL, United StatesKEYWORDSAlzheimer’s disease, dementia, neurotoxicants, N-nitrosodimethylamine (NDMA),copper, apolipoprotein E4, Heat Shock Protein 90 (Hsp90), metabolomicsEditorial on the Research TopicNeurotoxins in Alzheimer’s disease and other dementiasAlzheimer’s disease (AD) and other dementias are neurodegenerative disorderscharacterized by a progressive decline in cognition and independence from activities ofdaily living. Dementia is multifactorial with numerous risk factors including age, genes,molecules, lifestyle, and environmental contributions to disease onset and progression. Inrecent years, an emerging focus on neurotoxins has added a new layer of complexity to ourunderstanding of dementia. This editorial aims to discuss recent updates regarding the roleof neurotoxins in the pathogenesis of dementia.Copper’s double-edged swordCopper, a trace element crucial for various physiological processes, can accumulate inthe brain over time. The article “Copper and cuproptosis: New therapeutic approachesfor Alzheimer’s disease” reviews compelling evidence linking excessive free copperdeposition to cognitive decline in individuals with AD (Li et al.). Elevated freecopper levels in the serum and brain of AD patients lead to reduced antioxidantdefenses and mitochondrial dysfunction, setting the stage for neurodegeneration.Moreover, the accumulation triggers a specific form of cell death, known as copper-dependent cell death (cuproptosis). This revelation prompts a reevaluation of theintricate relationship between copper dysregulation and the progression of AD. Theefficacy and safety of interventions, such as copper chelators, lipid peroxidationinhibitors, and antioxidants, are also explored. These treatments aim to restore copperequilibrium and prevent copper-induced cell death in AD cases, offering a glimmer ofhope in the pursuit of pharmaceutical interventions to address copper dysregulation.Frontiers in AgingNeuroscience 01 frontiersin.orgHenriques et al. 10.3389/fnagi.2024.1363466NDMA’s stealthy entry into theAlzheimer’s puzzleN-nitrosodimethylamine (NDMA), an environmental and foodcontaminant, emerges as an unsuspected player in the neurotoxinrepertoire considering it is a widely recognized carcinogen. Thestudy “Association of N-nitrosodimethylamine exposure withcognitive impairment based on the clues of mice and humans”investigates the concentration of NDMA in foods and its effectson both murine and human cognition (Liu et al.). The findingssuggest an association between NDMA and cognitive decline,providing a new perspective on the environmental factors that maycontribute to AD. This study opens avenues for further researchinto the potential link between environmental carcinogens andneurodegenerative disorders.Apolipoprotein E4: unraveling thegenetic threadApolipoprotein E4 (ApoE4) is the largest genetic risk variantfor developing late-onset Alzheimer’s disease. The protein plays anessential role in providing cholesterol and other lipids for neuronalutilization. “Neuronal ApoE4 in Alzheimer’s disease and potentialtherapeutic targets” explores the role of ApoE4 in the developmentand progression of AD (Zhang et al.). This review emphasizeshow ApoE4 in neurons induces amyloid beta (Aβ) and tau proteinpathologies, leading to neuroinflammation and neuronal damage.Understanding the pathophysiology of neuronal ApoE4 becomescrucial in developing targeted therapeutic strategies to mitigate therisk of AD development.Hsp90 modulators: a molecularapproachThe presence of misfolded proteins in neurodegenerativediseases brings attention toward the dysregulation of molecularchaperones. “Protection against Aβ-induced neuronal damageby KU-32: PDHKI inhibition as important target” introducesnovobiocin, a modulator at the C-terminal ATP-binding site ofHeat Shock Protein 90 (Hsp90) (Pal et al.). The study exploresthe effects of novobiocin analogs, specifically focusing on KU-32, in protecting neurons from Aβ-induced death. This approachnot only highlights potential therapeutic avenues but also shedslight on the intricate relationship between protein misfolding andAD pathology.Metabolomics: elucidating smallmolecules impactMetabolomics provides a powerful tool for comprehensivelymeasuring low-molecular-weight molecules from biologicalsamples. The study “Metabolomic profiling of CSF and bloodserum elucidates general and sex-specific patterns for mildcognitive impairment and Alzheimer’s disease patients” quantifiesmetabolites in cerebrospinal fluid and serum, revealing significantalterations associated with dementia (Berezhnoy et al.). Reducedlevels of ketone bodies, branched-chain amino acids, andalterations in valine degradation pathways in AD patients highlightthe metabolic shifts in the disease. The study underscores thepotential of metabolomics in uncovering novel biomarkers andtherapeutic targets for AD.Aβ1–42 oligomers: enticing seizuresusceptibilityHyperactive neuronal networks and seizures are present inAD patients and genetic animal models. Although Aβ is anestablished biomarker for AD, its role in seizure susceptibilityremains unclear. “The intracerebral injection of Aβ1−42 oligomersdoes not invariably alter seizure susceptibility in mice” examinesthe effects of oligomeric Aβ1−42 on seizure susceptibility inNMRI outbred mice (Vande Vyver et al.). While ex vivo slicework highlights a biological role for Aβ1−42 on hippocampalhyperactivity, no effects after intracerebral injection were observedin vivo. The in vivo outcomes diverge from other research findings,underscoring the significance of conducting comprehensivebiophysical characterizations of Aβ1−42 for meaningful crossstudy comparisons.ConclusionIn conclusion, the neurotoxin landscape in Alzheimer’s diseaseis multifaceted, involving elements of copper dysregulation,environmental contaminants, genetic factors, molecularchaperones, metabolic shifts, and Aβ1−42 oligomers. Thiseditorial aims to coalesce these diverse areas of research intoa comprehensive narrative that contributes to our evolvingunderstanding of AD. As the puzzle pieces come together, the hopeis that these insights will pave the way for targeted interventionsand therapeutic strategies in the pursuit of optimized precisionmedicine for those suffering from all forms of dementia.Author contributionsAH:Writing – review& editing. PP:Writing – review& editing.BF: Writing – review & editing. KH: Writing – original draft.FundingThe author(s) declare that no financial support was received forthe research, authorship, and/or publication of this article.Conflict of interestAH and PP were employed by Neuro-Sys.The remaining authors declare that the research was conductedin the absence of any commercial or financial relationships thatcould be construed as a potential conflict of interest.The author(s) declared that they were an editorial boardmember of Frontiers, at the time of submission. This had no impacton the peer review process and the final decision.Frontiers in AgingNeuroscience 02 frontiersin.orgHenriques et al. 10.3389/fnagi.2024.1363466Publisher’s noteAll claims expressed in this article are solely those of theauthors and do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteed orendorsed by the publisher.Frontiers in AgingNeuroscience 03 frontiersin.org

Editorial: Neurotoxins in Alzheimer\u27s disease and other dementias

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Editorial: Neurotoxins in Alzheimer\u27s disease and other dementias

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