Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses

Aging and Disease, Год журнала: 2023, Номер unknown

Опубликована: Авг. 8, 2023

Alzheimer's disease (AD) is a prevalent neurodegenerative characterized by both amnestic and non-amnestic clinical manifestations. It accounts for approximately 60-70% of all dementia cases worldwide. With the increasing number AD patients, elucidating underlying mechanisms developing corresponding interventional strategies are necessary. Hypotheses about such as amyloid cascade, Tau hyper-phosphorylation, neuroinflammation, oxidative stress, mitochondrial dysfunction, cholinergic, vascular hypotheses not mutually exclusive, them play certain role in development AD. The cascade hypothesis currently most widely studied; however, other also gaining support. This article summarizes recent evidence regarding major pathological their potential interplay, well strengths weaknesses each implications effective treatments. could stimulate further studies promote more therapeutic

Язык: Английский

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Exercise therapy to prevent and treat Alzheimer’s disease

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Авг. 4, 2023

Alzheimer’s disease (AD) is a progressive neurodegenerative in the elderly with dementia, memory loss, and severe cognitive impairment that imposes high medical costs on individuals. The causes of AD include increased deposition amyloid beta (Aβ) phosphorylated tau, age, mitochondrial defects, neuroinflammation, decreased synaptic connections, nerve growth factors (NGF). While animals moderate-intensity exercise restores hippocampal amygdala through levels p-AKT, p-TrkB, p-PKC Aβ, tau phosphorylation, precursor proteins (APP) AD. Aerobic (with an intensity 50–75% VO2 max) prevents volume reduction, spatial learning reduction increasing flexibility. Exercise training induces binding brain-derived neurotrophic factor (BDNF) to TrkB NGF TrkA induce cell survival neuronal plasticity. After aerobic high-intensity interval training, increase VEGF, angiopoietin 1 2, NO, tPA, HCAR1 cerebral vessels blood flow angiogenesis cerebellum, motor cortex, striatum, hippocampus. In hippocampus, decreases fragmentation, DRP1, FIS1, improving OPA1, MFN1, MFN2, morphology. humans, acute as anti-inflammatory condition IL-6 such IL-1RA IL-10. Moderate-intensity also inhibits inflammatory markers IFN-γ, IL-1β, IL-6, CRP, TNF-α, sTNFR1, COX-2, NF-κB. significantly increases plasma BDNF, factor, plasticity, activity, memory, exploratory behavior subjects. Irisin myokine released from skeletal muscle during protects hippocampus by suppressing Aβ accumulation promoting proliferation STAT3 signaling. Therefore, combined strength balance coordination social activities seems provide important benefits for people

Язык: Английский

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The concept of resilience to Alzheimer’s Disease: current definitions and cellular and molecular mechanisms

Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)

Опубликована: Апрель 8, 2024

Abstract Some individuals are able to maintain their cognitive abilities despite the presence of significant Alzheimer’s Disease (AD) neuropathological changes. This discrepancy between cognition and pathology has been labeled as resilience evolved into a widely debated concept. External factors such stimulation associated with AD, but exact cellular molecular underpinnings not completely understood. In this review, we discuss current definitions used in field, highlight translational approaches investigate AD summarize underlying substrates that have derived from human animal studies, which received more attention last few years. From these studies picture emerges resilient different patients terms specific pathological species reaction pathology, possibly helps up certain tipping point. Studying rare can be great importance it could pave way novel therapeutic avenues for AD.

Язык: Английский

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Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer’s disease

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Фев. 2, 2024

Abstract Neuroinflammation is a pathological hallmark of Alzheimer’s disease (AD), characterized by the stimulation resident immune cells brain and penetration peripheral cells. These inflammatory processes facilitate deposition amyloid-beta (Aβ) plaques abnormal hyperphosphorylation tau protein. Managing neuroinflammation to restore homeostasis decrease neuronal damage therapeutic approach for AD. One way achieve this through exercise, which can improve function protect against neuroinflammation, oxidative stress, synaptic dysfunction in AD models. The neuroprotective impact exercise regulated various molecular factors that be activated same as administration their mimetics. Recent evidence has proven some mimetics effective alleviating AD, and, additionally, they are helpful alternative option patients who unable perform regular physical manage neurodegenerative disorders. This review focuses on current state knowledge mimetics, including efficacy, regulatory mechanisms, progress, challenges, limitations, future guidance application therapy.

Язык: Английский

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The immunological perspective of major depressive disorder: unveiling the interactions between central and peripheral immune mechanisms

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Янв. 19, 2025

Major depressive disorder is a prevalent mental disorder, yet its pathogenesis remains poorly understood. Accumulating evidence implicates dysregulated immune mechanisms as key contributors to disorders. This review elucidates the complex interplay between peripheral and central components underlying pathology. Peripherally, systemic inflammation, gut dysregulation, dysfunction in organs including gut, liver, spleen adipose tissue influence brain function through neural molecular pathways. Within nervous system, aberrant microglial astrocytes activation, cytokine imbalances, compromised blood-brain barrier integrity propagate neuroinflammation, disrupting neurotransmission, impairing neuroplasticity, promoting neuronal injury. The crosstalk immunity creates vicious cycle exacerbating neuropathology. Unraveling these multifaceted immune-mediated provides insights into major disorder's pathogenic basis potential biomarkers targets. Modulating both responses represent promising multidimensional therapeutic strategy.

Язык: Английский

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Understanding the mechanisms of disease modifying effects of aerobic exercise in people with Alzheimer’s disease

Ageing Research Reviews, Год журнала: 2024, Номер 94, С. 102202 - 102202

Опубликована: Янв. 23, 2024

Язык: Английский

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Potential Biomarkers and Treatment of Neuroinflammation in Parkinson's Disease

Actas Españolas de Psiquiatría, Год журнала: 2025, Номер 53(1), С. 181 - 188

Опубликована: Янв. 5, 2025

Parkinson's disease (PD) is a degenerative of the central nervous system primarily affecting middle-aged and elderly individuals, significantly compromising their quality life. Neuroinflammation now recognized as key feature in pathogenesis PD. This study reviews recent advances identification potential biomarkers associated with neuroinflammation PD significance for therapeutic strategies. These findings suggest that inflammatory factors play pivotal role treatment, interventions involving anti-inflammatory drugs, physical exercise, dietary modifications have shown promising results mitigating progression.

Язык: Английский

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Associations of modifiable dementia risk factors with dementia and cognitive decline: evidence from three prospective cohorts

Frontiers in Public Health, Год журнала: 2025, Номер 13

Опубликована: Янв. 15, 2025

This study aims to assess the relationship between modifiable dementia risk factors and both cognitive decline. Data were obtained from Health Retirement Study (HRS) [2008-2020], China Longitudinal (CHARLS) [2011-2020], English of Ageing (ELSA) [2010-2020]. After adjusting for confounding factors, multivariable logistic regression was utilized analyze dementia, while linear employed examine these Additionally, Cox proportional hazards model used number factor events, clusters, risk. A total 30,113 participants HRS, CHARLS, ELSA included (44.6% male, mean age 66.04 years), with an average follow-up period 7.29 years. low education level significantly associated increased accelerated decline (Overall, OR = 2.93, 95% CI: 2.70-3.18; Overall, β -0.25, -0.60 to-0.55). The presence multiple correlated a higher risk; Specifically, compared more than 5 having no only one lower HR 0.15, 0.11-0.22, 0.22, 0.18-0.25). Compared group coexistence clusters excessive alcohol, diabetes, vision loss, hearing loss (HR 4.11; CI 3.42-4.95; p < 0.001); smoking, 5.18; 4.30-6.23; obesity, smoking 5.96; 5.11-6.95; 0.001) most strongly Among 11 educational attainment has greatest impact on dose-response exists events is risk, associations vary by cluster.

Язык: Английский

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Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases

Frontiers in Physiology, Год журнала: 2024, Номер 15

Опубликована: Май 16, 2024

Neurodegenerative diseases are debilitating nervous system disorders attributed to various conditions such as body aging, gene mutations, genetic factors, and immune disorders. Prominent neurodegenerative include Alzheimer's disease, Parkinson's Huntington's amyotrophic lateral sclerosis, multiple sclerosis. Insulin resistance refers the inability of peripheral central tissues respond insulin effectively regulate blood sugar levels. has been observed in suggested induce occurrence, development, exacerbation diseases. Furthermore, an increasing number studies have that reversing may be a critical intervention for treatment Among numerous measures available improve sensitivity, exercise is widely accepted strategy due its convenience, affordability, significant impact on sensitivity. This review examines association between highlights molecular mechanisms by which can reverse under these conditions. The focus was regulating through providing practical ideas suggestions future research focused exercise-induced sensitivity context

Язык: Английский

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Polymeric nanocomposite electrode for enhanced electrochemical detection of α-lipoic acid: Application in neuroinflammation prevention and clinical analysis

Environmental Research, Год журнала: 2023, Номер 245, С. 117369 - 117369

Опубликована: Окт. 10, 2023

Язык: Английский

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