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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Macrophage migration inhibitor factor (MIF): Potential role in cognitive impairment disorders

Cytokine & Growth Factor Reviews, Год журнала: 2024, Номер 77, С. 67 - 75

Опубликована: Март 19, 2024

Язык: Английский

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Volume loss in the left anterior‐superior subunit of the hypothalamus in amyotrophic lateral sclerosis

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(6)

Опубликована: Июнь 1, 2024

Amyotrophic lateral sclerosis (ALS) causes motor neuron loss and progressive paralysis. While traditionally viewed as disease (MND), ALS also affects non-motor regions, such the hypothalamus. This study aimed to quantify hypothalamic subregion volumes in patients with versus healthy controls (HCs) examine their associations demographic clinical features.

Язык: Английский

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Non-motor symptoms in patients with amyotrophic lateral sclerosis: current state and future directions

Journal of Neurology, Год журнала: 2024, Номер 271(7), С. 3953 - 3977

Опубликована: Май 28, 2024

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of both upper and lower motor neurons. A defining histopathological feature in approximately 97% all ALS cases accumulation phosphorylated trans-activation response (TAR) DNA-binding protein 43 (pTDP-43) aggregates cytoplasm neurons glial cells within central nervous system. Traditionally, it was believed that TDP-43 subsequent neurodegeneration primarily occurs However, contemporary evidence suggests as progresses, other systems brain regions are also affected. Despite this, there has been limited number clinical studies assessing non-motor symptoms patients. These often employ various outcome measures, resulting wide range reported frequencies The importance reflects fact they have significant impact on patients' quality life, yet frequently go underdiagnosed unreported during evaluations. This review aims to provide an up-to-date overview current knowledge concerning ALS. Furthermore, we address their diagnosis treatment everyday practice.

Язык: Английский

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Resting-State EEG Oscillations in Amyotrophic Lateral Sclerosis (ALS): Toward Mechanistic Insights and Clinical Markers

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(2), С. 545 - 545

Опубликована: Янв. 16, 2025

Introduction: Amyotrophic lateral sclerosis (ALS) is a complex, progressive neurodegenerative disorder characterized by the degeneration of motor neurons in brain, brainstem, and spinal cord. Several neuroimaging techniques can help reveal pathophysiology ALS. One these electroencephalogram (EEG), noninvasive relatively inexpensive tool for examining electrical activity brain with excellent temporal precision. Methods: This mechanistic review examines pattern resting-state EEG activity. With focus on publications published between January 1995 October 2024, we carried out comprehensive search 2024 across number databases, including PubMed/Medline, Research Gate, Google Scholar, Cochrane. Results: The literature yielded 17 studies included this review. varied significantly their methodology patient characteristics. Despite this, common biomarker typical ALS was found-reduced alpha power. Regarding other oscillations, findings are less consistent sometimes contradictory. As review, three possible explanations provided. main most important one increased cortical excitability. In addition, due to limitations studies, recommendations future research topic outlined enable further better understanding patterns Conclusions: Most showed power deficits patients, reflecting pathological hyperexcitability cerebral cortex. Future should address methodological identified small sample sizes, inconsistent frequency-band definitions, insufficient functional outcome measures, solidify extend current findings.

Язык: Английский

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Cognitive reserve as a modulator of cognitive decline and of behavioral symptoms in patients with amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Год журнала: 2024, Номер 25(7-8), С. 726 - 736

Опубликована: Авг. 5, 2024

Introduction: Amyotrophic lateral sclerosis (ALS) has heterogeneous manifestations ranging from motor neuron degeneration to cognitive and behavioral impairment. This study aims clarify the interactions between cognition symptoms with relevant disease predictors reserve (CR), quantified through education, physical activity, occupation proxies. Methods: A prospective sample of 162 ALS patients 61 controls were evaluated Edinburgh Cognitive Behavioral Screen (ECAS) (dependent variable), a Reserve Index questionnaire (CRIq) demographic data (age sex), and, for patients, clinical variables: duration, site onset, Functional Rating Scale (ALSFRS), forced vital capacity (FVC), gene mutation chromosome 9 open reading frame 72 (C9orf72) (independent variables). Multiple regression mediation analyses performed predict symptoms. Results: For group, statistical model explained 38.8% variance in ECAS total (p < 0.001), 59.4% executive functions 55% 0.001). controls, it accounted 52.8% Interaction effects analysis showed CR is an modulator, differential effect within groups Verbal fluency was single best score differentiate = 0.004), C9orf72 found be symptom' predictor 0.009). Conclusion: supports proposed concept that acts as modulator healthy individuals. Moreover, also modulates ALS.

Язык: Английский

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Insights into Dysregulated Neurological Biomarkers in Cancer

Cancers, Год журнала: 2024, Номер 16(15), С. 2680 - 2680

Опубликована: Июль 27, 2024

The link between neurodegenerative diseases (NDs) and cancer has generated greater interest in biomedical research, with decades of global studies investigating biomarkers to better understand possible connections. Tau, amyloid-β, α-synuclein, SOD1, TDP-43, other proteins associated nervous system have also been identified various types solid malignant tumors, suggesting a potential overlap pathological processes. In this review, we aim provide an overview current evidence on the role these cancer, specifically examining their effects cell proliferation, apoptosis, chemoresistance, tumor progression. Additionally, discuss diagnostic therapeutic implications interconnection, emphasizing importance further research completely comprehend clinical tumors. Finally, explore challenges opportunities targeting for development new targeted anticancer therapies, providing insight into how integrate knowledge NDs oncology research.

Язык: Английский

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Cognitive function in amyotrophic lateral sclerosis: a cross-sectional and prospective pragmatic clinical study with review of the literature

Neurological Sciences, Год журнала: 2023, Номер 45(5), С. 2075 - 2085

Опубликована: Дек. 18, 2023

Abstract Background Amyotrophic lateral sclerosis (ALS) can present with either bulbar or spinal symptoms, and in some cases, both types of symptoms may be present. In addition, cognitive impairment has been observed ALS. The study aimed to evaluate the frontal general performance ALS not only cross-sectionally but also longitudinally. Methods materials Frontal Assessment Battery (FAB) Montreal Cognitive (MoCA) were employed assess function 52 adults cognitively healthy individuals. statistical analyses encompassed Pearson Chi square test, Skillings-Mack Spearman’s rank correlation coefficient, Proportional Odds Logistic Regression Model (POLR). Results Cross-sectionally, lower was associated diagnosis, older age, motor functional decline. individuals spinal-bulbar showed faster deterioration compared those symptoms. subgroup consistently performed worst delayed recall attention, while subgroups exhibited inferior scores recall, visuospatial skills, orientation, verbal fluency. Conclusion incorporation screening diagnostic workup beneficial, as early detection enhance symptom management improve quality life for their care partners.

Язык: Английский

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Smell loss is associated with cognitive impairment in amyotrophic lateral sclerosis patients

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(7)

Опубликована: Июль 1, 2024

Abstract Background Smell loss significantly impacts the quality of life in patients. However, there is limited research on smell individuals with amyotrophic lateral sclerosis (ALS), and correlation between cognitive impairment unclear. This study aimed to investigate cognition ALS Methods The included 216 Edinburgh Cognitive Behavioural Screen (ECAS) identification test specifically for Chinese population (CSIT) were administered evaluate participants' olfactory function, respectively. Results After covarying age, sex, BMI, education level, degree hunger, dietary bias, eagerness food, stress, smoking status, alcohol consumption, upper respiratory tract infection (URTI) or rhinitis, CSIT scores correlated ECAS ( r = 0.162, p 0.028), especially ALS‐specific 0.158, 0.031). Even after excluding patients URTI results similar. 0.224, 0.011), 0.205, 0.019). Conclusion In ALS, impairment, particularly frontotemporal dysfunction. dysfunction may lead worse performance

Язык: Английский

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Psychological resilience is protective against cognitive deterioration in motor neuron diseases

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Год журнала: 2024, Номер 25(7-8), С. 717 - 725

Опубликована: Авг. 13, 2024

Recent studies suggest that psychological resilience (PR) is associated with more well-preserved cognition in healthy subjects (HS), but an investigation of such phenomenon patients motor neuron diseases (MNDs) still lacking. The aim our study was therefore to evaluate PR and its relationship baseline cognitive/behavioral mood symptoms, as well longitudinal cognitive functioning, MNDs.

Язык: Английский

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