Sex and gender differences in cognitive resilience to aging and Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(8), P. 5695 - 5719

Published: July 5, 2024

Abstract Sex and gender—biological social constructs—significantly impact the prevalence of protective risk factors, influencing burden Alzheimer's disease (AD; amyloid beta tau) other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding interplay these factors is central to understanding resilience resistance mechanisms explaining maintained function reduced pathology accumulation in aging AD. In this narrative review, ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach provide foundations recommendations for future research into sex‐ gender‐specific drivers resilience, including sex/gender‐oriented review genetics, AD non‐AD pathologies, brain structure function, animal research. We urge field adopt sex/gender‐aware advance our intricate biological determinants consider sex/gender‐specific throughout stages. Highlights differences decline vary by age status. Initial evidence supports sex‐specific distinctions pathology. Findings suggest sex on cognition. There change transition clinical Gender warrant study: modifiable, immune, inflammatory, vascular.

Language: Английский

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Glial cell alterations in diabetes-induced neurodegeneration

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 18, 2024

Abstract Type 2 diabetes mellitus is a global epidemic that due to its increasing prevalence worldwide will likely become the most common debilitating health condition. Even if primarily metabolic disorder, it now well established key aspects of pathogenesis are associated with nervous system alterations, including deleterious chronic inflammation neural tissues, referred here as neuroinflammation, along different detrimental glial cell responses stress conditions and neurodegenerative features. Moreover, resembles accelerated aging, further risk developing age-linked disorders. As such, disabling diabetic comorbidities, namely retinopathy, peripheral neuropathy, cognitive decline, intimately neurodegeneration. described in aging other neurological disorders, alterations such microglial, astrocyte, Müller increased reactivity dysfunctionality, myelin loss Schwann have been broadly both human animal models, where they contributors noxious tissues within PNS CNS. In this review, we aim describe in-depth unique underlying changes observed across three main complications, goal uncovering shared cells pathological mechanisms enable discovery potential targets limit neuroinflammation prevent neurodegeneration all complications. Diabetes complications already public concern rapidly incidence, thus economic impact. Hence, understanding role play decline provide us novel therapeutic approaches tackle diabetic-associated Graphical abstract

Language: Английский

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Clonally expanded, targetable, natural killer-like NKG7 T cells seed the aged spinal cord to disrupt myeloid-dependent wound healing

Neuron, Journal Year: 2025, Volume and Issue: 113(5), P. 684 - 700.e8

Published: Jan. 13, 2025

Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed intact human murine spinal multiply further after injury. NKLT accumulate in via C-X-C motif chemokine receptor 6 ligand 16 signaling to clonally expand by engaging with major histocompatibility complex (MHC)-I-expressing myeloid cells. expressing killer cell granule protein 7 (Nkg7) disrupt myeloid-cell-dependent wound healing injured cord. Nkg7 deletion mice curbs degranulation normalize phenotype, thus promoting repair axonal integrity. Monoclonal antibodies neutralizing CD8+ SCI enhance neurological recovery healing. Our results unveil a reversible role for NKG7+CD8+ exacerbating damage, suggesting clinically relevant treatment SCI.

Language: Английский

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AIF1: Function and Connection with Inflammatory Diseases

Biology, Journal Year: 2023, Volume and Issue: 12(5), P. 694 - 694

Published: May 9, 2023

Macrophages are a type of immune cell distributed throughout all tissues an organism. Allograft inflammatory factor 1 (AIF1) is calcium-binding protein linked to the activation macrophages. AIF1 key intracellular signaling molecule that participates in phagocytosis, membrane ruffling and F-actin polymerization. Moreover, it has several type-specific functions. plays important roles development diseases: kidney disease, rheumatoid arthritis, cancer, cardiovascular diseases, metabolic diseases neurological disorders, transplants. In this review, we present comprehensive review known structure, functions role diseases.

Language: Английский

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The neurotransmitter puzzle of Alzheimer's: Dissecting mechanisms and exploring therapeutic horizons

Brain Research, Journal Year: 2024, Volume and Issue: 1829, P. 148797 - 148797

Published: Feb. 10, 2024

Language: Английский

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Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 3, 2024

Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability the development of secondary neurodegenerative diseases. A holistic understanding mechanisms controlling responses specific types their crosstalk is required develop an efficient strategy better regeneration. Here, we combine spatial single-cell transcriptomics chart transcriptomic signature injured male murine cerebral cortex, identify states different cells contributing this signature. Interestingly, distinct share large fraction injury-regulated genes, including inflammatory programs downstream innate immune-associated pathways Cxcr3 Tlr1/2. Systemic manipulation these decreases reactivity state associated with poor The functional relevance discovered shared highlights importance our resource enabling comprehensive analysis early events after injury.

Language: Английский

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Microglia, Trem2, and Neurodegeneration

The Neuroscientist, Journal Year: 2024, Volume and Issue: unknown

Published: May 20, 2024

Microglia are a specialized type of neuroimmune cells that undergo morphological and molecular changes through multiple signaling pathways in response to pathological protein aggregates, neuronal death, tissue injury, or infections. express Trem2, which serves as receptor for multitude ligands enhancing their phagocytic activity. Trem2 has emerged critical modulator microglial activity, especially many neurodegenerative disorders. Human TREM2 mutations associated with an increased risk developing Alzheimer disease (AD) other diseases. plays dual roles neuroinflammation more specifically disease-associated microglia. Most recent developments on the mechanisms emphasizing its role uptake clearance amyloid β (Aβ) aggregates debris help protect preserve brain, encouraging. Although normally stimulates defense mechanisms, dysregulation can intensify inflammation, poses major therapeutic challenges. Recent approaches targeting via agonistic antibodies gene therapy methodologies present possible avenues reducing burden This review highlights promise target, Aβ-associated AD, calls mechanistic investigations understand context-specific effective therapies against

Language: Английский

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Functional and Therapeutic Potential of Cynara scolymus in Health Benefits

Nutrients, Journal Year: 2024, Volume and Issue: 16(6), P. 872 - 872

Published: March 17, 2024

Dietary supplements enriched with bioactive compounds represent a promising approach to influence physiological processes and enhance longevity overall health. Cynara cardunculus var. scolymus serves as functional food supplement high concentration of compounds, which offers various health-promoting benefits. Several chronic diseases have metabolic, genetic, or inflammatory origins, are frequently interconnected. Pharmacological treatments, although effective, often result in undesirable side effects. In this context, preventive approaches gaining increased attention. Recent literature indicates that the consumption diet can positively organism’s biological functions. Polyphenols, well-known for their health benefits, widely recognized valuable preventing/combating pathologies related lifestyle, metabolism, aging. The C. belonging Asteraceae family, is used herbal medicine fields its beneficial properties. Although inflorescences (capitula) artichoke culinary purposes, preparations based on leaves be an active ingredient medicines. shows potential benefits different domains. Its nutritional value make it candidate improving well-being. exhibits anti-inflammatory, antioxidant, liver-protective, bile-expelling, antimicrobial, lipid-lowering neuroprotective Different studies demonstrate oxidative stress leading cause onset progression major human disorders such cardiovascular, neurological, cancer diseases. large amount polyphenol found has antioxidant activity, enabling neutralize free radicals, preventing cellular damage. This reduces subsequent risk developing conditions cancer, diabetes, cardiovascular Additionally, these polyphenols anti-inflammatory closely associated As result, contribute treatment diseases, including intestinal disorders, neurodegenerative pathologies. current review discussed profiles, pharmacological effects scolymus.

Language: Английский

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Microglia: a promising therapeutic target in spinal cord injury

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(2), P. 454 - 463

Published: April 16, 2024

Microglia are present throughout the central nervous system and vital in neural repair, nutrition, phagocytosis, immunological regulation, maintaining neuronal function. In a healthy spinal cord, microglia accountable for immune surveillance, however, when cord injury occurs, microenvironment drastically changes, leading to glial scars failed axonal regeneration. this context, vary their gene protein expression during activation, proliferation reaction injury, influencing responses both favorably unfavorably. A dynamic multifaceted response is mediated by microglia, which interact directly with neurons, astrocytes, oligodendrocytes, stem/progenitor cells. Despite clear understanding of essential nature origin, mechanisms action new functions require extensive research. This review summarizes current studies on microglial genesis, physiological function, pathological state, highlights crucial roles proposes as therapeutic target.

Language: Английский

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The role of short-chain fatty acids in central nervous system diseases: A bibliometric and visualized analysis with future directions

Heliyon, Journal Year: 2024, Volume and Issue: 10(4), P. e26377 - e26377

Published: Feb. 1, 2024

Short-chain fatty acids (SCFAs) are thought to play a key role in the microbe-gut-brain axis and involve pathogenesis of variety neurological diseases. This study aimed identify research hotspots evolution trends SCFAs central nervous diseases (CNS) examine current trends.

Language: Английский

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