Roles of Oxidative Stress in Synaptic Dysfunction and Neuronal Cell Death in Alzheimer’s Disease

Antioxidants, Год журнала: 2023, Номер 12(8), С. 1628 - 1628

Опубликована: Авг. 17, 2023

Alzheimer’s disease (AD) is a brain disorder that progressively undermines memory and thinking skills by affecting the hippocampus entorhinal cortex. The main histopathological hallmarks of AD are presence abnormal protein aggregates (Aβ tau), synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA RNA defects, inflammation, neuronal cell death. However, oxidative stress or damage also evident commonly overlooked considered consequence advancement dementia symptoms. control onset linked to activity amyloid-β peptide, which may serve as both antioxidant pro-oxidant molecules. Furthermore, correlated with proteins, nucleic acids, lipids in vulnerable populations, ultimately lead death through different molecular mechanisms. By recognizing an integral feature AD, alternative therapeutic preventive interventions developed tested potential complementary therapies for this devastating neurodegenerative disease.

Язык: Английский

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The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet for the Aging Brain: A Systematic Review

Advances in Nutrition, Год журнала: 2024, Номер 15(3), С. 100184 - 100184

Опубликована: Фев. 3, 2024

The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet seems a promising approach preserve brain function during aging. Previous systematic reviews have demonstrated benefits of the MIND cognition and dementia, though an update is needed. Additionally, other outcomes relevant aging not been summarized. Therefore, this review aims give up-to-date complete overview on human studies that examined in relation adults aged ≥40 y. Ovid Medline, Web Science core collection, Scopus were searched up July 25, 2023. Study quality was assessed using Newcastle-Ottawa Scale Cochrane Risk-of-Bias tool. We included 40 articles, which 32 unique cohorts. Higher adherence protective dementia 7 10 positive associations 3 4 cohorts global 6 episodic memory. effects cognitive decline are less apparent, with only 2 longitudinal demonstrating 1 memory decline. For (domain-specific cognition, impairments, Parkinson's disease, volume, pathology), results mixed or few had performed. Many North American origin, raising question if most favorable healthy population-dependent. In conclusion, provides observational evidence between risk, but remains and/or limited. may be preferred populations, populations conclusive. This registered at PROSPERO as CRD42022254625.

Язык: Английский

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The Integral Role of Magnesium in Muscle Integrity and Aging: A Comprehensive Review

Nutrients, Год журнала: 2023, Номер 15(24), С. 5127 - 5127

Опубликована: Дек. 16, 2023

Aging is characterized by significant physiological changes, with the degree of decline varying significantly among individuals. The preservation intrinsic capacity over course an individual's lifespan fundamental for healthy aging. Locomotion, which entails independent movement, intricately connected various dimensions human life, including cognition, vitality, sensory perception, and psychological well-being. Notably, skeletal muscle functions as a pivotal nexus within this intricate framework. Any perturbation in its functionality can manifest compromised physical performance elevated susceptibility to frailty. Magnesium essential mineral that plays central role approximately 800 biochemical reactions body. Its distinctive chemical attributes render it indispensable stabilizing factor orchestration diverse cellular organelle functions, thereby rendering irreplaceable processes directly impacting health. This narrative review offers comprehensive exploration played magnesium maintaining integrity, emphasizing critical importance optimal levels promoting

Язык: Английский

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Breaking down the cellular responses to type I interferon neurotoxicity in the brain

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 3, 2023

Since their original discovery, type I interferons (IFN-Is) have been closely associated with antiviral immune responses. However, biological functions go far beyond this role, balanced IFN-I activity being critical to maintain cellular and tissue homeostasis. Recent findings uncovered a darker side of IFN-Is whereby chronically elevated levels induce devastating neuroinflammatory neurodegenerative pathologies. The underlying causes these ‘interferonopathies’ are diverse include monogenetic syndromes, autoimmune disorders, as well chronic infections. prominent involvement the CNS in disorders indicates particular susceptibility brain cells toxicity. Here we will discuss current knowledge how mediate neurotoxicity by analyzing cell-type specific responses CNS, secondly, exploring spectrum neurological arising from increased IFN-Is. Understanding nature is crucial fundamental step towards development new therapeutic strategies for interferonopathies.

Язык: Английский

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Anti-Inflammatory Effects of Flavonoids in Common Neurological Disorders Associated with Aging

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4297 - 4297

Опубликована: Фев. 21, 2023

Aging reduces homeostasis and contributes to increasing the risk of brain diseases death. Some principal characteristics are chronic low-grade inflammation, a general increase in secretion proinflammatory cytokines, inflammatory markers. Aging-related include focal ischemic stroke neurodegenerative such as Alzheimer’s disease (AD) Parkinson’s (PD). Flavonoids most common class polyphenols abundantly found plant-based foods beverages. A small group individual flavonoid molecules (e.g., quercetin, epigallocatechin-3-gallate, myricetin) has been used explore anti-inflammatory effect vitro studies animal models AD PD, results show that these reduce activated neuroglia several also, inactivate inflammation inflammasome-related transcription factors. However, evidence from human limited. In this review article, we highlight natural can modulate neuroinflammation diverse clinical discuss future areas research help researchers develop new therapeutic agents.

Язык: Английский

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New Pathways Identify Novel Drug Targets for the Prevention and Treatment of Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5383 - 5383

Опубликована: Март 11, 2023

Alzheimer’s disease (AD) is an incurable, progressive neurodegenerative disorder. AD a complex and multifactorial that responsible for 60–80% of dementia cases. Aging, genetic factors, epigenetic changes are the main risk factors AD. Two aggregation-prone proteins play decisive role in pathogenesis: β-amyloid (Aβ) hyperphosphorylated tau (pTau). Both them form deposits diffusible toxic aggregates brain. These biomarkers Different hypotheses have tried to explain pathogenesis served as platforms drug research. Experiments demonstrated both Aβ pTau might start processes necessary cognitive decline. The two pathologies act synergy. Inhibition formation has been old target. Recently, successful clearance by monoclonal antibodies raised new hopes treatments if detected at early stages. More recently, novel targets, e.g., improvements amyloid from brain, application small heat shock (Hsps), modulation chronic neuroinflammation different receptor ligands, microglial phagocytosis, increase myelination revealed

Язык: Английский

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The Dynamic Relationship between the Glymphatic System, Aging, Memory, and Sleep

Biomedicines, Год журнала: 2023, Номер 11(8), С. 2092 - 2092

Опубликована: Июль 25, 2023

The process of memory entails the activation numerous neural networks and biochemical pathways throughout brain. phenomenon decline in relation to aging has been subject extensive research for several decades. correlation between is intricate various aspects consider. Throughout process, there are alterations that take place within brain and, as expected, affect other functions have already linked its function such involving microcirculation sleep. Recent studies provide an understanding how these mechanisms may be interconnected through relatively new concept glymphatic system. system strongly correlated sleep processes. Sleep helps remove waste solutes. Astrocytes expand contract form channels cerebrospinal fluid (CSF) wash eliminate waste. However, details not totally elusive, but discovery what we call enables us connect many pieces physiology understand factors interplay them. Thus, purpose this review discuss system, sleep, memory, a network complex dynamic interactions.

Язык: Английский

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Molecular hallmarks of ageing in amyotrophic lateral sclerosis

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Март 2, 2024

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal, severely debilitating and rapidly progressing disorder affecting motor neurons in the brain, brainstem, spinal cord. Unfortunately, there are few effective treatments, thus remains critical need to find novel interventions that can mitigate against its effects. Whilst aetiology of ALS unclear, ageing major risk factor. Ageing slowly progressive process marked by functional decline an organism over lifespan. However, it unclear how promotes ALS. At molecular cellular level specific hallmarks characteristic normal ageing. These highly inter-related overlap significantly with each other. Moreover, whilst process, striking similarities at between these factors neurodegeneration Nine were originally proposed: genomic instability, loss telomeres, senescence, epigenetic modifications, dysregulated nutrient sensing, proteostasis, mitochondrial dysfunction, stem cell exhaustion, altered inter-cellular communication. recently (2023) expanded include dysregulation autophagy, inflammation dysbiosis. Hence, given latest updates hallmarks, their close association disease processes ALS, new examination relationship pathophysiology warranted. In this review, we describe possible mechanisms which impacts on neurodegenerative implicated therapeutic may arise from this.

Язык: Английский

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Neural correlates of obesity across the lifespan

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Май 28, 2024

Abstract Associations between brain and obesity are bidirectional: changes in structure function underpin over-eating, while chronic adiposity leads to atrophy. Investigating brain-obesity interactions across the lifespan can help better understand these relationships. This study explores interaction cortical morphometry children, young adults, older adults. We also investigate genetic, neurochemical, cognitive correlates of associations. Our findings reveal a pattern lower thickness fronto-temporal regions associated with all age cohorts varying age-dependent patterns remaining regions. In adults neurochemical expression inflammatory mitochondrial genes. children is modifications involved emotional attentional processes. Thus, might originate from during early adolescence, leading neurodegeneration later life through mechanisms.

Язык: Английский

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Single-nucleus transcriptomic profiling of human orbitofrontal cortex reveals convergent effects of aging and psychiatric disease

Nature Neuroscience, Год журнала: 2024, Номер 27(10), С. 2021 - 2032

Опубликована: Сен. 3, 2024

Abstract Aging is a complex biological process and represents the largest risk factor for neurodegenerative disorders. The disorders also increased in individuals with psychiatric Here, we characterized age-related transcriptomic changes brain by profiling ~800,000 nuclei from orbitofrontal cortex 87 without diagnoses replicated findings an independent cohort 32 individuals. affects all cell types, LAMP5 + LHX6 interneurons, cell-type abundant primates, far most affected. Disrupted synaptic transmission emerged as convergently affected pathway aged tissue. Age-related overlapped observed Alzheimer’s disease across multiple types. We find evidence accelerated aging demonstrate converging signature of psychopathology Our shed light on cell-type-specific effects pathways underlying their convergence driven diagnosis.

Язык: Английский

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