Hypoxia and brain aging: Neurodegeneration or neuroprotection?

Ageing Research Reviews, Год журнала: 2021, Номер 68, С. 101343 - 101343

Опубликована: Апрель 16, 2021

The absolute reliance of the mammalian brain on oxygen to generate ATP renders it acutely vulnerable hypoxia, whether at high altitude or in clinical settings anemia pulmonary disease. Hypoxia is pivotal pathogeneses myriad neurological disorders, including Alzheimer's, Parkinson's and other age-related neurodegenerative diseases. Conversely, reduced environmental oxygen, e.g. sojourns residing altitudes, may impart favorable effects aging mortality. Moreover, controlled hypoxia exposure represent a treatment strategy for disorders. This review discusses evidence hypoxia's beneficial vs. detrimental impacts molecular mechanisms that mediate these divergent effects. It draws upon an extensive literature search hypoxia/altitude aging, detailed analysis all identified studies directly comparing responses young aged humans rodents. Special attention directed toward risks benefits elderly, potential therapeutic applications Finally, important questions future research are discussed.

Язык: Английский

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Mechanistic insights and perspectives involved in neuroprotective action of quercetin

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 140, С. 111729 - 111729

Опубликована: Май 25, 2021

Neurodegenerative diseases (NDDs) are the primary cause of disabilities in elderly people. Growing evidence indicates that oxidative stress, mitochondrial dysfunction, neuroinflammation and apoptosis associated with aging basis most neurodegenerative disorders. Quercetin is a flavonoid significant pharmacological effects promising therapeutic potential. It widely distributed among plants typically found daily diets mainly fruits vegetables. shows number biological properties connected to its antioxidant activity. Neuroprotection by quercetin has been reported many vitro as well vivo studies. However, exact mechanism action still mystery similarly there hypothesis exploring neuroprotection. enhances neuronal longevity neurogenesis modulating inhibiting wide pathways. This review assesses food sources quercetin, pharmacokinetic profile, structure activity relationship pathophysiological role various NDDs it also provides synopsis literature between downstream signalling pathways modulated for neuroprotection eg. nuclear factor erythroid 2-related 2 (Nrf2), Paraoxonase-2 (PON2), c-Jun N-terminal kinase (JNK), Tumour Necrosis Factor alpha (TNF-α), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α), Sirtuins, Mitogen-activated protein kinases (MAPKs) cascades, CREB (Cyclic AMP response element binding protein) Phosphoinositide 3- kinase(PI3K/Akt). Therefore, aim present was elaborate on cellular molecular mechanisms involved protection against NDDs.

Язык: Английский

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Alzheimer’s Disease: An Update and Insights Into Pathophysiology

Frontiers in Aging Neuroscience, Год журнала: 2022, Номер 14

Опубликована: Март 30, 2022

Alzheimer’s disease (AD) is an irreversible brain disorder associated with slow, progressive loss of functions mostly in older people. The processes start years before the symptoms are manifested at which point most therapies may not be as effective. In hippocampus, key proteins involved JAK2/STAT3 signaling pathway, such p-JAK2-Tyr1007 and p-STAT3-Tyr705 were found to elevated various models AD. addition neurons, glial cells astrocytes also play a crucial role progression Without having significant effect on tau amyloid pathologies, pathway reactive exhibits behavioral impact experimental Cholinergic atrophy AD has been traced trophic failure NGF metabolic essential for survival maintenance basal forebrain cholinergic neurons (BFCN). AD, there alteration conversion proNGF mature (mNGF), increase degradation biologically active mNGF. Thus, application exogenous mNGF studies was shown improve recovery atrophic BFCN. Furthermore, it now coming light that FGF7/FGFR2/PI3K/Akt mediated by microRNA-107 pathogenesis. Vascular dysfunction long cognitive decline increased risk factors higher cerebral beta-amyloid (Aβ) burden, while synergistically acting Aβ induce decline. apolipoprotein E4 polymorphism just one vascular factors, but prevalent genetic factor More recently, research focus shifted toward metabolisms neurotransmitters, major minor nutrients, thus giving rise metabolomics, important “omics” tool diagnosis prognosis neurodegenerative diseases based individual’s metabolome. This review will therefore proffer better understanding novel pathways neural mechanisms elaborate potential links between recent developments “omics”-based biomarkers

Язык: Английский

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Apoptotic Pathways and Alzheimer’s Disease: Probing Therapeutic Potential

Neurochemical Research, Год журнала: 2021, Номер 46(12), С. 3103 - 3122

Опубликована: Авг. 12, 2021

Язык: Английский

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Signal pathways in the treatment of Alzheimer’s disease with traditional Chinese medicine

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 152, С. 113208 - 113208

Опубликована: Май 31, 2022

This study aimed to reveal the classical signal pathways and important potential targets of traditional Chinese medicine (TCM) for treating Alzheimer's disease (AD), provide support further investigation on TCM its active ingredients.Literature survey was conducted using PubMed, Web Science, Google Scholar, CNKI, other databases, with "Alzheimer's disease," "traditional medicine," "medicinal herb," "Chinese "natural plant" as primary keywords.TCM could modulate related AD pathological progression, including NF-κB, Nrf2, JAK/STAT, ubiquitin-proteasome pathway, autophagy-lysosome pathway-related AMPK/mTOR, GSK-3/mTOR, PI3K/Akt/mTOR, well SIRT1 PPARα pathway. It regulate crosstalk between through a multitarget, thus maintaining chronic inflammatory interaction balance, inhibiting oxidative stress damage, regulating system function, modulating autophagy, eventually improving cognitive impairment in patients AD.TCM be multilevel, multitargeted, multifaceted prevent treat AD. In-depth research prevention treatment new ideas exploring pathogenesis developing anti-AD drugs.

Язык: Английский

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Salidroside attenuates neuronal ferroptosis by activating the Nrf2/HO1 signaling pathway in Aβ1-42-induced Alzheimer’s disease mice and glutamate-injured HT22 cells

Chinese Medicine, Год журнала: 2022, Номер 17(1)

Опубликована: Июль 4, 2022

Alzheimer's disease (AD) is a neurodegenerative disease. Ferroptosis plays critical role in diseases. Nuclear factor E2-related 2 (Nrf2) considered an important ferroptosis. Studies have demonstrated that salidroside has potential therapeutic effect on AD. The intrinsic of ferroptosis unclear. purpose this study was to investigate the protective effects and pharmacological mechanisms alleviating neuronal Aβ1-42-induced AD mice glutamate-injured HT22 cells.HT22 cells were injured by glutamate (Glu), transfected with siRNA Nrf2, WT Nrf2-/-AD treated salidroside. mitochondria ultrastructure, intracellular Fe2+, reactive oxygen species, mitochondrial membrane potential, lipid peroxidation detected. Malondialdehyde, reduced glutathione, oxidized glutathione disulfide, superoxide dismutase measured. novel object recognition test, Y-maze, open field test used mice. protein expressions PTGS2, GPX4, HO1 hippocampus investigated Western blot.Salidroside increased cell viability level MMP Glu-injured cells, ROS, GPX4 SLC7A11 expressions. These changes not observed Nrf2 cells. Salidroside improved ultrastructural mice, but expression levels HO1, NQO1 decreased PTGS2 mice.Salidroside neuroprotective inhibiting its mechanism related activation Nrf2/HO1 signaling pathway.

Язык: Английский

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Dysbiosis and Alzheimer’s Disease: A Role for Chronic Stress?

Biomolecules, Год журнала: 2021, Номер 11(5), С. 678 - 678

Опубликована: Апрель 30, 2021

Alzheimer’s disease (AD) is an incurable, neuropsychiatric, pathological condition that deteriorates the worth of geriatric lives. AD characterized by aggregated senile amyloid plaques, neurofibrillary tangles, neuronal loss, gliosis, oxidative stress, neurotransmitter dysfunction, and bioenergetic deficits. The changes in GIT composition harmony have been recognized as a decisive interesting player pathologies including AD. Microbiota control influence oxidoreductase status, inflammation, immune system, endocrine system through which it may impact on cognitive domain. altered malfunctioned state microbiota associated with minor infections to complicated illnesses include psychosis neurodegeneration, several studies show regulates plasticity development. (dysbiosis) affect behavior, stress response, functions. Chronic stress-mediated progression also has well-defined role intermingles at various physiological levels directly impacts advancement stress-modulated alterations well-established markers but gut–brain axis mediation downstream signaling mechanisms modulate microbial commensals GIT. extensive literature reports chronic stressors composition, metabolic activities, capacities. present manuscript aims elucidate mechanistic pathways induces dysbiosis, turn escalates neuropathological cascade stress–dysbiosis appears feasible zone work direction treatment

Язык: Английский

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Therapeutic benefits of flavonoids against neuroinflammation: a systematic review

Inflammopharmacology, Год журнала: 2022, Номер 30(1), С. 111 - 136

Опубликована: Янв. 15, 2022

Язык: Английский

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Targeting protein kinases for the treatment of Alzheimer's disease: Recent progress and future perspectives

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 261, С. 115817 - 115817

Опубликована: Сен. 14, 2023

Язык: Английский

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Neuroprotective effect of tangeretin against chromium-induced acute brain injury in rats: targeting Nrf2 signaling pathway, inflammatory mediators, and apoptosis

Inflammopharmacology, Год журнала: 2023, Номер 31(3), С. 1465 - 1480

Опубликована: Март 8, 2023

Abstract Potassium dichromate (PD) is an environmental xenobiotic commonly recognized as teratogenic, carcinogenic, and mutagenic in animals humans. The present study was conducted to investigate the role of tangeretin (TNG) a neuro-protective drug against PD-induced brain injury rats. Thirty-two male adult Wistar rats were blindly divided into four groups (8 rats/group). first group received saline intranasally (i.n.). second single dose PD (2 mg/kg, i.n.). third TNG (50 mg/kg; orally), for 14 days followed by i.n. on last day experiment. fourth (100 orally) Behavioral indices evaluated 18 h after administration. Neuro-biochemical histopathological studies 24 Results revealed that intoxicated with induced- oxidative stress inflammation via increase malondialdehyde (MDA) decrease nuclear factor erythroid 2-related 2 (Nrf2) signaling pathway glutathione(GSH) levels contents tumor necrosis factor-alpha (TNF-α) interleukin (IL-6). Pre-treatment ameliorated behavior, cholinergic activities, decreased elevated pro-inflammatory mediators; TNF-α IL-6 content chromium residues detected Plasma–Optical Emission Spectrometer. Also, picture improved significantly mg/kg). Additionally, caspase-3 expression In conclusion, possesses significant neuroprotective acute modulating Nrf2 quenching release inflammatory mediators apoptosis Graphical abstract

Язык: Английский

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