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Molecular and Cellular Mechanism in Alzheimer's Disease

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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: closed (31 December 2023) | Viewed by 9455

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Special Issue Editor

Dr. Eva Bagyinszky

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Guest Editor

Department of Industrial and Environmental Engineering, Graduate School of Environment, Gachon University, Seongnam 13120, Republic of Korea
Interests: bioinformatics; neuroscience; molecular biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alzheimer’s disease (AD) is one of the most common forms of neurodegeneration; it mostly affects elderlies. However, several individuals develop disease phenotypes under 65 years of age. AD is a growing health concern as the number of patients is increasing rapidly. Even though promising findings are available on disease therapies, currently, there is no drug is available that can stop or revert AD-related neurodegeneration.

Several AD-related biomarkers (genetic, transcriptomic, or proteomic) and candidates have been discovered, which may aid in further tackling the disease. Microglia has been verifed to play a significant role in brain development and could protect against neurodegeneration. Impaired microglia and abnormal activity of amyloid deposits may result in an elevated risk for AD progression. The role of gut microbiota has also been investigated in neurodegenerative diseases, including AD.

In this Special Issue of the International Journal of Molecular Sciences, the main topics will be the “Molecular and Cellular Mechanism in Alzheimer's Disease”. Research, review articles, and case reports that are dedicated to different AD-related studies are welcome:

Identification of genetic factors and candidates that may impact Alzheimer’s disease progression.
Promising biomarkes, which could improve disease diagnosis, or the differential diagnoses between AD and other neurodegenerative diseases.
Alzheimer’s disease and microglia. The neuroinflammation and oxidative stress-related disease mechanisms/pathways.
AD and microbiota.

Dr. Eva Bagyinszky
Guest Editor

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 submissions that pass pre-check are 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

genetic risk factors
proteomic biomarkers
transcriptomics
microglia
oxidative stress
microbiota
diagnosis
therapy
Alzheimer’s disease
neurodegeneration

Published Papers (4 papers)

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Research

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17 pages, 2683 KiB

Open AccessArticle

Neuroprotection and Mechanism of Gas-miR36-5p from Gastrodia elata in an Alzheimer’s Disease Model by Regulating Glycogen Synthase Kinase-3β

by Zhongteng Lu, Jianyuan Fu, Guang Wu, Zhecheng Yang, Xiaoqi Wu, Dan Wang, Zhengying You, Zuoming Nie and Qing Sheng

Int. J. Mol. Sci. 2023, 24(24), 17295; https://doi.org/10.3390/ijms242417295 - 09 Dec 2023

Cited by 1 | Viewed by 864

Abstract

Alzheimer’s disease (AD) is currently the most common neurodegenerative disease. Glycogen synthase kinase 3β (GSK-3β) is a pivotal factor in AD pathogenesis. Recent research has demonstrated that plant miRNAs exert cross-kingdom regulation on the target genes in animals. Gastrodia elata (G. elata) is a valuable traditional Chinese medicine that has significant pharmacological activity against diseases of the central nervous system (CNS). Our previous studies have indicated that G. elata-specific miRNA plays a cross-kingdom regulatory role for the NF-κB signaling pathway in mice. In this study, further bioinformatics analysis suggested that Gas-miR36-5p targets GSK-3β. Through western blot, RT-qPCR, and assessments of T-AOC, SOD, and MDA levels, Gas-miR36-5p demonstrated its neuroprotective effects in an AD cell model. Furthermore, Gas-miR36-5p was detected in the murine brain tissues. The results of the Morris water maze test and western blot analysis provided positive evidence for reversing the learning deficits and hyperphosphorylation of Tau in AD mice, elucidating significant neuroprotective effects in an AD model following G. elata RNA administration. Our research emphasizes Gas-miR36-5p as a novel G. elata-specific miRNA with neuroprotective properties in Alzheimer’s disease by targeting GSK-3β. Consequently, our findings provide valuable insights into the cross-kingdom regulatory mechanisms underlying G. elata-specific miRNA, presenting a novel perspective for the treatment of Alzheimer’s disease. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanism in Alzheimer's Disease)

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25 pages, 2312 KiB

Open AccessArticle

The Cleavage-Specific Tau 12A12mAb Exerts an Anti-Amyloidogenic Action by Modulating the Endocytic and Bioenergetic Pathways in Alzheimer’s Disease Mouse Model

by Valentina Latina, Anna Atlante, Francesca Malerba, Federico La Regina, Bijorn Omar Balzamino, Alessandra Micera, Annabella Pignataro, Egidio Stigliano, Sebastiano Cavallaro, Pietro Calissano and Giuseppina Amadoro

Int. J. Mol. Sci. 2023, 24(11), 9683; https://doi.org/10.3390/ijms24119683 - 02 Jun 2023

Cited by 3 | Viewed by 2007

Abstract

Beyond deficits in hippocampal-dependent episodic memory, Alzheimer’s Disease (AD) features sensory impairment in visual cognition consistent with extensive neuropathology in the retina. 12A12 is a monoclonal cleavage specific antibody (mAb) that in vivo selectively neutralizes the AD-relevant, harmful N-terminal 20–22 kDa tau fragment(s) (i.e., NH₂htau) without affecting the full-length normal protein. When systemically injected into the Tg2576 mouse model overexpressing a mutant form of Amyloid Precursor Protein (APP), APPK670/671L linked to early onset familial AD, this conformation-specific tau mAb successfully reduces the NH₂htau accumulating both in their brain and retina and, thus, markedly alleviates the phenotype-associated signs. By means of a combined biochemical and metabolic experimental approach, we report that 12A12mAb downregulates the steady state expression levels of APP and Beta-Secretase 1 (BACE-1) and, thus, limits the Amyloid beta (Aβ) production both in the hippocampus and retina from this AD animal model. The local, antibody-mediated anti-amyloidogenic action is paralleled in vivo by coordinated modulation of the endocytic (BIN1, RIN3) and bioenergetic (glycolysis and L-Lactate) pathways. These findings indicate for the first time that similar molecular and metabolic retino-cerebral pathways are modulated in a coordinated fashion in response to 12A12mAb treatment to tackle the neurosensorial Aβ accumulation in AD neurodegeneration. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanism in Alzheimer's Disease)

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Review

Jump to: Research

15 pages, 1265 KiB

Open AccessReview

The Molecular Mechanisms of Neuroinflammation in Alzheimer’s Disease, the Consequence of Neural Cell Death

by Su-Bin Choi, Sehee Kwon, Ji-Hye Kim, Na-Hyun Ahn, Joo-Hee Lee and Seung-Hoon Yang

Int. J. Mol. Sci. 2023, 24(14), 11757; https://doi.org/10.3390/ijms241411757 - 21 Jul 2023

Cited by 2 | Viewed by 2086

Abstract

Alzheimer’s disease (AD) is accompanied by neural cell loss and memory deficit. Neural cell death, occurring via apoptosis and autophagy, is widely observed in the AD brain in addition to neuroinflammation mediated by necroptosis and the NLRP3 inflammasome. Neurotoxicity induced by amyloid-beta (Aβ) and tau aggregates leads to excessive neural cell death and neuroinflammation in the AD brain. During AD progression, uncontrolled neural cell death results in the dysregulation of cellular activity and synaptic function. Apoptosis mediated by pro-apoptotic caspases, autophagy regulated by autophagy-related proteins, and necroptosis controlled by the RIPK/MLKL axis are representative of neural cell death occurred during AD. Necroptosis causes the release of cellular components, contributing to the pro-inflammatory environment in the AD brain. Inordinately high levels of neural cell death and pro-inflammatory events lead to the production of pro-inflammatory cytokines and feed-forward hyper neuroinflammation. Thus, neural cell death and neuroinflammation cause synaptic dysfunction and memory deficits in the AD brain. In this review, we briefly introduce the mechanisms of neural cell death and neuroinflammation observed in the AD brain. Combined with a typical strategy for targeting Aβ and tau, regulation of neural cell death and neuroinflammation may be effective for the amelioration of AD pathologies. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanism in Alzheimer's Disease)

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21 pages, 1267 KiB

Open AccessReview

Presenilin-1 (PSEN1) Mutations: Clinical Phenotypes beyond Alzheimer’s Disease

by Youngsoon Yang, Eva Bagyinszky and Seong Soo A. An

Int. J. Mol. Sci. 2023, 24(9), 8417; https://doi.org/10.3390/ijms24098417 - 08 May 2023

Cited by 8 | Viewed by 4080

Abstract

Presenilin 1 (PSEN1) is a part of the gamma secretase complex with several interacting substrates, including amyloid precursor protein (APP), Notch, adhesion proteins and beta catenin. PSEN1 has been extensively studied in neurodegeneration, and more than 300 PSEN1 mutations have been discovered to date. In addition to the classical early onset Alzheimer’s disease (EOAD) phenotypes, PSEN1 mutations were discovered in several atypical AD or non-AD phenotypes, such as frontotemporal dementia (FTD), Parkinson’s disease (PD), dementia with Lewy bodies (DLB) or spastic paraparesis (SP). For example, Leu113Pro, Leu226Phe, Met233Leu and an Arg352 duplication were discovered in patients with FTD, while Pro436Gln, Arg278Gln and Pro284Leu mutations were also reported in patients with motor dysfunctions. Interestingly, PSEN1 mutations may also impact non-neurodegenerative phenotypes, including PSEN1 Pro242fs, which could cause acne inversa, while Asp333Gly was reported in a family with dilated cardiomyopathy. The phenotypic diversity suggests that PSEN1 may be responsible for atypical disease phenotypes or types of disease other than AD. Taken together, neurodegenerative diseases such as AD, PD, DLB and FTD may share several common hallmarks (cognitive and motor impairment, associated with abnormal protein aggregates). These findings suggested that PSEN1 may interact with risk modifiers, which may result in alternative disease phenotypes such as DLB or FTD phenotypes, or through less-dominant amyloid pathways. Next-generation sequencing and/or biomarker analysis may be essential in clearly differentiating the possible disease phenotypes and pathways associated with non-AD phenotypes. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanism in Alzheimer's Disease)

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