The Role of Mitochondrial Calcium Homeostasis in Alzheimer’s and Related Diseases

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(23), P. 9153 - 9153

Published: Dec. 1, 2020

Calcium signaling is essential for neuronal function, and its dysregulation has been implicated across neurodegenerative diseases, including Alzheimer's disease (AD). A close reciprocal relationship exists between calcium mitochondrial function. Growing evidence in a variety of AD models indicates that dyshomeostasis drastically alters activity which, turn, drives neurodegeneration. This review discusses the potential pathogenic mechanisms by which impairs function AD, focusing on impact endoplasmic reticulum (ER)-mitochondrial communication, transport, oxidative stress, protein homeostasis. also summarizes recent data highlight need exploring underlying calcium-mediated dysfunction while suggesting targets modulating levels to treat diseases such as AD.

Language: Английский

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Discovery of novel benzophenone integrated derivatives as anti-Alzheimer’s agents targeting presenilin-1 and presenilin-2 inhibition: A computational approach

PLoS ONE, Journal Year: 2022, Volume and Issue: 17(4), P. e0265022 - e0265022

Published: April 8, 2022

The most commonly accepted hypothesis of Alzheimer's disease (AD) is the amyloid caused due to formation accumulation Aβ42 isoform, which leads neurodegeneration. In this regard, presenilin-1 (PSEN-1) and -2 (PSEN-2) proteins play a crucial role by altering precursor protein (APP) metabolism, affecting γ-secretase protease secretion, finally leading increased levels Aβ. absence reported commercial pharmacotherapeutic agents targeting presenilins, we aim propose benzophenone integrated derivatives (BIDs) as potential inhibitors presenilin through in silico approach. study evaluates interaction BIDs molecular docking simulations, dynamics binding free energy calculations. This first ever computational approach discover proteins. It also comprises druglikeliness analysis compounds. Out all screened BIDs, BID-16 was found be lead compound against both Based on these results, one can evaluate an anti-Alzheimer's specifically near future using vitro vivo methods.

Language: Английский

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Latest advances in mechanisms of epileptic activity in Alzheimer’s disease and dementia with Lewy Bodies

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 8, 2024

Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) stand as the prevailing sources of neurodegenerative dementia, impacting over 55 million individuals across globe. Patients AD DLB exhibit a higher prevalence epileptic activity compared to those other forms dementia. Seizures can accompany in early stages, associated contribute cognitive symptoms exacerbate decline. Aberrant neuronal may be caused by several mechanisms that are not yet understood. Hyperexcitability could biomarker for detection or before onset In this review, we compare contrast network hyperexcitability DLB. We examine contributions genetic risk factors, Ca 2+ dysregulation, glutamate, AMPA NMDA receptors, mTOR, pathological amyloid beta, tau α-synuclein, altered microglial astrocytic activity, impaired inhibitory interneuron function. By gaining deeper understanding molecular cause hyperexcitability, might uncover therapeutic approaches effectively ease slow down advancement

Language: Английский

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A Combinational Therapy for Preventing and Delaying the Onset of Alzheimer’s Disease: A Focus on Probiotic and Vitamin Co-Supplementation

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 202 - 202

Published: Feb. 5, 2024

Alzheimer’s disease is a progressive neurodegenerative disorder with complex etiology, and effective interventions to prevent or delay its onset remain global health challenge. In recent years, there has been growing interest in the potential role of probiotic vitamin supplementation as complementary strategies for prevention. This review paper explores current scientific literature on use probiotics vitamins, particularly A, D, E, K, B-complex context prevention management. We delve into mechanisms through which may modulate gut–brain interactions neuroinflammation while vitamins play crucial roles neuronal cognitive function. The also examines collective impact this combinational therapy reducing risk factors associated disease, such oxidative stress, inflammation, gut dysbiosis. By providing comprehensive overview existing evidence mechanisms, aims shed light promise co-supplementation multifaceted approach combat offering insights possible avenues future research clinical application.

Language: Английский

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Alzheimer's disease: a comprehensive review of epidemiology, risk factors, symptoms diagnosis, management, caregiving, advanced treatments and associated challenges

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 16, 2024

Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired reasoning. It the leading cause of dementia in older adults, marked pathological accumulation amyloid-beta plaques neurofibrillary tangles. These changes lead to widespread neuronal damage, significantly impacting daily functioning quality life.

Language: Английский

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Periodontal Pathogens and Associated Intrathecal Antibodies in Early Stages of Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2018, Volume and Issue: 66(1), P. 105 - 114

Published: Sept. 11, 2018

Background: Recent studies suggest a link between periodontitis and Alzheimer’s disease (AD). Objective: Verification of the presence periodontal pathogens intrathecal generation pathogen-specific antibodies in 20 patients with AD other forms dementia (DEM-noAD). Methods: Clinical indices were recorded. Cerebrospinal fluid (CSF) was analyzed for total tau protein (T-tau) amyloid-β (Aβ 1-42 ). In serum CSF, antibody levels against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Treponema species quantified. The selected bacteria inflammatory biomarkers determined periodontium, serum, CSF. Results: line diagnoses, CSF-levels Aβ significantly lower than DEM-noAD patients. Periodontal destruction inflammation omnipresent no difference groups. P. T. forsythia, detected more 50% subgingival biofilm samples, but neither nor Elevated anti-pathogen CSF 16 (7 AD; 9 DEM-noAD) compared to highlight possibility immune response pathogens. There significant Multivariate regression analysis general linear models revealed an association T-tau level group both anti- gingivalis MCP-1/CCL-2. Conclusion: may enter brain stimulate local response. However, at age up 70 years, do not act as trigger developing AD.

Language: Английский

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Genetic Markers of Alzheimer’s Disease

Advances in experimental medicine and biology, Journal Year: 2019, Volume and Issue: unknown, P. 27 - 52

Published: Jan. 1, 2019

Language: Английский

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Modifiable, Non-Modifiable, and Clinical Factors Associated with Progression of Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2021, Volume and Issue: 80(1), P. 1 - 27

Published: Jan. 15, 2021

There is an extensive literature relating to factors associated with the development of Alzheimer’s disease (AD), but less known about which may contribute its progression. This review examined regard 15 were suggested by PubMed search be positively cognitive and/or neuropathological progression AD. The grouped as potentially modifiable (vascular risk factors, comorbidities, malnutrition, educational level, inflammation, and oxidative stress), non-modifiable (age at clinical onset, family history dementia, gender, Apolipoprotein E ɛ4, genetic variants, altered gene regulation), (baseline neuropsychiatric symptoms, extrapyramidal signs). Although conflicting results found for majority a positive association was in nearly all studies investigated relationship six AD progression: regulation, baseline signs. Whether these or other have been actually influence rate decline patients unclear. Therapeutic approaches include addressing should considered.

Language: Английский

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AlCl3 induced learning and memory deficit in zebrafish

NeuroToxicology, Journal Year: 2022, Volume and Issue: 92, P. 67 - 76

Published: July 15, 2022

Language: Английский

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Urolithin A reduces amyloid-beta load and improves cognitive deficits uncorrelated with plaque burden in a mouse model of Alzheimer’s disease

GeroScience, Journal Year: 2022, Volume and Issue: 45(2), P. 1095 - 1113

Published: Dec. 28, 2022

Abstract In the present study, we investigated effects of urolithin A (UA), a metabolite generated from ellagic acid via its metabolism by gut bacteria, as an autophagy activator with potential neuroprotective activity. WT and 3xTg-AD mice were administered long-term intermittent dietary supplementation UA. UA was found to prevent deficits in spatial memory, cued fear response, exploratory behavior this model. It also decreased Aβ plaque burden areas hippocampus where these protein deposits are prominent Interestingly, correlation analyses demonstrate that positively correlates enhanced memory on control diet but not those supplemented contrast, Aβ42 abundance cortical hippocampal homogenates negatively correlate UA-fed mice. Our data suggest formation may be protective mechanism against neurodegeneration cognitive decline targeting generation proteotoxic species might more successful approach halting disease progression. extend lifespan normal aging Mechanistically, is able induce increase clearance neuronal cell lines. summary, our studies reveal UA, likely actions inducer, capable removing neurons administration prevents onset associated pathological deposition mouse model well extending

Language: Английский

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