Protective effects of mitophagy enhancers against amyloid beta-induced mitochondrial and synaptic toxicities in Alzheimer disease

Human Molecular Genetics, Год журнала: 2021, Номер 31(3), С. 423 - 439

Опубликована: Сен. 8, 2021

The purpose of our study is to determine the protective effects mitophagy enhancers against mutant APP and amyloid beta (Aβ)-induced mitochondrial synaptic toxicities in Alzheimer's disease (ad). Over two decades research from lab others revealed that abnormalities are largely involved pathogenesis both early-onset late-onset ad. Emerging studies impaired clearance dead or dying mitochondria an early event process. Based on these changes, it has been proposed potential therapeutic candidates treat patients with In current study, we optimized doses urolithin A, actinonin, tomatidine, nicotinamide riboside immortalized mouse primary hippocampal (HT22) neurons. We transfected HT22 cells cDNA treated assessed mRNA protein levels dynamics, biogenesis, genes, cell survival; respiration mAPP-HT22 untreated enhancers. also morphology Mutant APP-HT22 showed increased fission, decreased fusion, & reduced survival defective respiration, excessively fragmented length mitochondria. However, events were reversed mitophagy-enhancers-treated cells. Cell was significantly increased, genes number reduced, fragmentation Further, A strongest Aβ-induced findings, cautiously propose promising drugs

Язык: Английский

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Aperiodic and Periodic Components of Ongoing Oscillatory Brain Dynamics Link Distinct Functional Aspects of Cognition across Adult Lifespan

eNeuro, Год журнала: 2021, Номер 8(5), С. ENEURO.0224 - 21.2021

Опубликована: Сен. 1, 2021

Signal transmission in the brain propagates via distinct oscillatory frequency bands but aperiodic component, 1/f activity, almost always co-exists which most of previous studies have not sufficiently taken into consideration. We used a recently proposed parameterization model that delimits and components neural dynamics on lifespan aging data collected from human participants using magnetoencephalography (MEG). Since healthy underlines an enormous change local tissue properties, any systematic relationship activity would highlight their impact self-organized critical functional states. Furthermore, we patterns correlation between background metrics behavior to understand domain general effects activity. suggest age-associated global baseline alters states affecting information processing impacting critically all aspects cognition, e.g., metacognitive awareness, speed retrieval memory, cognitive load, accuracy recall through adult lifespan. This alteration crucially impacts features peak (PF) band power ratio, relates more selective during visual short-term memory (VSTM) task. In summary, this study leveraging big for first time tracks cross-sectional lifespan-associated periodic dynamical changes resting state demonstrate how normative PF, ratio (BR) measures provide insights about decline

Язык: Английский

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Mitophagy enhancers against phosphorylated Tau-induced mitochondrial and synaptic toxicities in Alzheimer disease

Pharmacological Research, Год журнала: 2021, Номер 174, С. 105973 - 105973

Опубликована: Ноя. 8, 2021

Язык: Английский

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Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer’s disease

Frontiers in Molecular Neuroscience, Год журнала: 2022, Номер 15

Опубликована: Авг. 25, 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder that one of the most devastating and widespread diseases worldwide, mainly affecting aging population. One key factors contributing to AD-related neurotoxicity production aggregation amyloid β (Aβ). Many studies have shown ability Aβ bind cell membrane disrupt its structure, leading death. Because damage affects different parts brain differently, it seems likely not only but also nature interface with which interacts, helps determine final neurotoxic effect. cholesterol dominant component plasma membrane, plays an important role in Aβ-induced toxicity. Elevated levels their regulation by statins been be influencing progression neurodegeneration. However, data from many has both neuroprotective aggravating effects relation development AD. In this review, we attempt summarize recent findings on toxicity mediated binding pathogenesis AD consider broader context lipid composition membranes.

Язык: Английский

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Insulin and Its Key Role for Mitochondrial Function/Dysfunction and Quality Control: A Shared Link between Dysmetabolism and Neurodegeneration

Biology, Год журнала: 2022, Номер 11(6), С. 943 - 943

Опубликована: Июнь 20, 2022

Insulin was discovered and isolated from the beta cells of pancreatic islets dogs is associated with regulation peripheral glucose homeostasis. produced in brain related to synaptic plasticity memory. Defective insulin signaling plays a role dysfunction, such as neurodegenerative disease. Growing evidence suggests link between metabolic disorders, diabetes obesity, diseases, especially Alzheimer’s disease (AD). This association due common state resistance (IR) mitochondrial dysfunction. review takes journey into past summarize what known about physiological pathological tissues brain. Then, it will land present analyze on health effects diseases that are IR-dependent. Specifically, we focus our attention quality control mitochondria (MQC), dynamics, biogenesis, selective autophagy (mitophagy), healthy altered cases. Finally, this be projected toward future by examining most promising treatments target cure disorders.

Язык: Английский

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Accumulation of APP-CTF induces mitophagy dysfunction in the iNSCs model of Alzheimer’s disease

Cell Death Discovery, Год журнала: 2022, Номер 8(1)

Опубликована: Янв. 10, 2022

Mitochondrial dysfunction is associated with familial Alzheimer's disease (fAD), and the accumulation of damaged mitochondria has been reported as an initial symptom that further contributes to progression. In amyloidogenic pathway, amyloid precursor protein (APP) cleaved by β-secretase generate a C-terminal fragment, which then γ-secretase produce amyloid-beta (Aβ). The Aβ its detrimental effect on mitochondrial function are well known, yet protein-derived fragments (APP-CTFs) contributing this pathology have rarely reported. We demonstrated effects APP-CTFs-related using induced neural stem cells (iNSCs) from AD patient-derived fibroblasts. APP-CTFs was mainly occur within domains be both cause consequence dysfunction. also resulted in mitophagy failure, validated increased LC3-II p62 inconsistent PTEN-induced kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) recruitment failed fusion lysosomes. causality impaired were verified patient-iNSCs. Furthermore, we confirmed pathological loop presenilin knockout iNSCs (PSEN KO-iNSCs) because due blockage similarly occurs presenilin-deficient cells. present work, report contribution failure patient-iNSCs PSEN KO-iNSCs.

Язык: Английский

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Are mitophagy enhancers therapeutic targets for Alzheimer’s disease?

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 149, С. 112918 - 112918

Опубликована: Апрель 4, 2022

Healthy mitochondria are essential for functional bioenergetics, calcium signaling, and balanced redox homeostasis. Dysfunctional a central aspect of aging neurodegenerative diseases such as Alzheimer's disease (AD). The formation accumulation amyloid beta (Aβ) hyperphosphorylated tau (P-tau) play large roles in the cellular changes seen AD, including mitochondrial dysfunction, synaptic damage, neuronal loss, defective mitophagy. Mitophagy is process whereby damaged selectively removed, it plays an important role quality control. associated with increased reactive oxygen species levels Aβ, P-tau Drp1, which together trigger mitophagy autophagy. Impaired causes progressive organelles mitochondria, has been hypothesized that restoration may offer therapeutic benefits to AD patients. This review highlights challenges pharmacologically inducing through two different signaling cascades: 1) PINK1/parkin-dependent pathway 2) PINK1/parkin-independent pathway, emphasis on abnormal interactions Aβ P-Tau, alter age-dependent manner. article also summarizes recent studies effects enhancers, urolithin A, NAD+, actinonin, tomatidine, mutant APP/Aβ Tau. Findings from our lab have revealed enhancers can suppress APP/Aβ-induced Tau-induced dysfunctions mouse cell line models AD. Finally, we discuss mechanisms underlying beneficial health like resveratrol spermidine

Язык: Английский

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Ergothioneine and its prospects as an anti-ageing compound

Experimental Gerontology, Год журнала: 2022, Номер 170, С. 111982 - 111982

Опубликована: Окт. 14, 2022

Healthy ageing is a crucial process that needs to be highlighted as it affects the quality of lifespan. An increase in oxidative stress along with major factor related age-associated diseases, especially neurodegenerative disorders. antioxidant-rich diet has been proven play significant role process. Targeting mechanisms could worthwhile approach improving health standards. Ergothioneine (EGT), hydrophilic compound specific transporter known OCTN1, shown exert anti-ageing properties. In addition its antioxidant effect, EGT reported have anti-senescence, anti-inflammatory and anti-neurodegenerative This review aims define pivotal signalling pathways such insulin/insulin-like growth (IGF) (IIS), sirtuin 6 (SIRT6) mammalian target rapamycin complex (mTOR) pathways. The further discusses evidence on neurodegeneration therapeutic context various model organisms, providing new insights into health. conclusion, an ergothioneine-rich may beneficial preventing age-related resulting healthy population.

Язык: Английский

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Targeting Mitochondrial Oxidative Stress as a Strategy to Treat Aging and Age-Related Diseases

Antioxidants, Год журнала: 2023, Номер 12(4), С. 934 - 934

Опубликована: Апрель 15, 2023

Mitochondria are one of the organelles undergoing rapid alteration during senescence process. Senescent cells show an increase in mitochondrial size, which is attributed to accumulation defective mitochondria, causes oxidative stress. Defective mitochondria also targets stress, and vicious cycle between stress contributes onset development aging age-related diseases. Based on findings, strategies reduce have been suggested for effective treatment In this article, we discuss alterations consequent Then, causal role investigated by examining how diseases exacerbated induced Furthermore, assess importance targeting regulation suggest different therapeutic Therefore, review will not only shed light a new perspective but provide through

Язык: Английский

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Urgent needs of caregiving in ageing populations with Alzheimer’s disease and other chronic conditions: Support our loved ones

Ageing Research Reviews, Год журнала: 2023, Номер 90, С. 102001 - 102001

Опубликована: Июль 5, 2023

Язык: Английский

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