Mitochondrial Calcium Signaling as a Therapeutic Target for Alzheimer’s Disease

Wu, Aston Jiaxi; Tong, Benjamin Chun‐Kit; Huang, Alexis Shiying; Li, Min; Cheung, King‐Ho

doi:10.2174/1567205016666191210091302

Cited by 21 publications

(8 citation statements)

References 176 publications

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“…The hippocampus is severely affected in diseases with neuroinflammatory components such as AD [ 14 ]. Significant memory loss and cognitive decline are associated with neuronal death and gray matter loss, especially in the frontal cortex and hippocampus [ 84 ]. The destruction of neuronal homeostasis determines irreversible degeneration and neuronal apoptosis.…”

Section: Ad Relation To the Cholinergic Systemmentioning

confidence: 99%

Role of Cholinergic Signaling in Alzheimer’s Disease

et al. 2022

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Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer’s disease (AD), a progressive and commonly diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.

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Section: Ad Relation To the Cholinergic Systemmentioning

confidence: 99%

Role of Cholinergic Signaling in Alzheimer’s Disease

et al. 2022

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“…Calcium overload can activate calcium-dependent proteases and nitric oxide synthase, destroy mitochondria, and result in neuronal excitotoxicity. , These effects might derive from the formation of ion channels within the cell membrane by toxic fragments of fibril Aβ, fostering a direct leakage of calcium into cells . Some studies have shown that several L-type calcium channel blockers may alleviate neuronal degeneration in early-stage AD therapy. , Therefore, in the above-mentioned mechanism investigation, the falcarinol-type analogues might act as targeted molecules for L-type calcium ion channels and play a blocking role in the upstream of the cell pathway.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Falcarinol-Type Analogues as Potential Calcium Channel Blockers

Tan

Guo

et al. 2021

J. Nat. Prod.

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A series of enantiomers of falcarinol analogues (2) were synthesized using a chiral 1,1′-binaphth-2-ol (BINOL)-based catalytic system. The neuroprotective effects of falcarinol (1a) and its analogues (2) on PC12 cells injured by sodium azide (NaN3) were investigated. The structure–function relationships and possible mechanism were studied. Pretreatment of PC12 cells with falcarinol analogues (R)-2d and (R)-2i for 1 h following addition of NaN3 and culture in a CO2 incubator for 24 h resulted in significant elevation of cell viability, as determined by a CCK-8 assay and Hoechst staining, with reduction of LDH release and MDA content, increase of SOD activity, and decrease of ROS stress, when compared with the activity of natural falcarinol (1a). These observations indicated that the falcarinol analogues (R)-2d and (R)-2i can protect PC12 cells against NaN3-induced apoptosis via increasing resistance to oxidative stress. For the first time, falcarinol (1a) and its analogue (R)-2i were found to have potential L-type calcium channel-blocking activity, as recorded using a manual patch clamp technique on HEK-293 cells stably expressing hCav1.2 (α1C/β2a/α2δ1). These findings suggest that the mechanism of the L-type calcium channel-blocking activity of falcarinol (1a) and its analogue (R)-2i might be involved in neuroprotection by falcarinol-type analogues by inhibiting calcium overload in the upstream of the signaling pathway.

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“…Mitochondria absorb Ca 2+ at the expense of the electrochemical gradient generated during respiration. Mitochondrial Ca 2+ overload means high uptake of mitochondrial Ca 2+ which makes it easier to impair neuron functions and exacerbates AD progression by impairing mitochondrial respiration, increasing reactive oxygen species formation, inducing apoptosis, and damaging mitochondria recycling mitophagy ( Wu et al, 2020 ). Mitochondria are essential energy generators for tissue homeostasis and channels for programmed apoptosis and necrotic cell death.…”

Section: Introductionmentioning

confidence: 99%

Trends of mitochondrial changes in AD: a bibliometric study

Song

Guo

et al. 2023

Front. Aging Neurosci.

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BackgroundAlzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive progress and memory loss, which eventually develops into dementia. It can cause personality disorders and decreased quality of life of patients. Currently, AD patients account for 60–70% of global dementia patients and the incidence rate of AD is increasing annually. AD not only causes pain to patients but also brings a heavy burden to the entire family. Studies have found that there is a connection between mitochondrial dysfunction and other biochemical changes in AD like classical neuropathological hallmarks (β-amyloid and tau protein), inflammation pathways, oxidative stress, and so on. Evidence shows that early treatment targeted directly to mitochondria could extend the lifespan of model mice and decrease the relevant neuropathological markers. Therefore, research on the mitochondrial dysfunction of AD can be of potential significance for clinical treatment. To date, few bibliometric analysis articles related to mitochondrial dysfunction of AD have been published. Bibliometric analysis refers to quantitatively analyzing certain aspects of articles like publishers, authors, and countries by using statistical and mathematical methods. Combined with statistical software, a large number of papers can be converted to visualization figures and tables, which provide vital information such as keyword hotspots and the names of contributing authors. Through the bibliometric analysis method, our study aimed to provide study trends and keyword hotpots for researchers to conduct further relevant research in this field.MethodsWe used the Web of Science core collection database as a literature retrieval tool to obtain data related to mitochondrial changes in Alzheimer’s disease during the last 20 years. The retrieval type was [TS = (Alzheimer’s disease)] ND [TS = (mitochondrion)], ranging from January 1, 2000 to June 30, 2022. VOSviewer v1.6.18, Arcgis 10.8, and HistCite pro 2.1 were used to conduct data visualization analysis. VOSviewer v1.6.18 made relevant network visualization maps of the cooperative relationship between relevant countries, institutions, and authors (co-authorship), the frequency of different keywords appearing together (co-occurrence), and the frequency of different articles cited together (co-cited). Arcgis 10.8 created the world map of publications distribution in this field and Histcite pro 2.1 was used to count the local citation score (LCS) of references. In addition, Journal Citation Reports were used to consult the latest journal import factor and JCI quartile.ResultsAs of June 30, 2022, from the Web of Science core collection, we selected 2,474 original articles in English, excluding the document types of the news items, meeting abstracts, and some articles that had little relevance to our theme. The United States acted as the leader and enjoyed a high reputation in this field. The University of California System was the institution that made the greatest contribution (3.64% with 90 papers). Most articles were published in the Journal of Alzheimer’s Disease (8.21%, with 203 papers). The most frequently co-cited journal in Q1 was the Journal of Biological Chemistry (8,666 citations, TLS: 1039591). Russel H. Swerdlow (55 publications) was the most productive author and PH Reddy was the most co-cited author with 1,264 citations (TLS: 62971). The hotpots of mitochondrial dysfunction in AD were as follows: “oxidative stress,” “amyloid-beta-protein,” “tau,” “apoptosis,” “inflammation,” “autophagy,” “precursor protein,” “endoplasmic-reticulum,” “dynamics” and “mitochondrial unfolded protein response.”ConclusionThis bibliometric analysis research will help readers rapidly identify current hotpots and milestone studies related to directions of interest in AD research.

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Mitochondrial Calcium Signaling as a Therapeutic Target for Alzheimer’s Disease

Cited by 21 publications

References 176 publications

Role of Cholinergic Signaling in Alzheimer’s Disease

Role of Cholinergic Signaling in Alzheimer’s Disease

Synthesis and Biological Evaluation of Falcarinol-Type Analogues as Potential Calcium Channel Blockers

Trends of mitochondrial changes in AD: a bibliometric study

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