Implication of Central Nervous System Barrier Impairment in Amyotrophic Lateral Sclerosis: Gender-Related Difference in Patients DOI Open Access
Hugo Alarcan, Patrick Vourc’h,

Lise Berton

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 11196 - 11196

Опубликована: Июль 7, 2023

Central nervous system (CNS) barrier impairment has been reported in amyotrophic lateral sclerosis (ALS), highlighting its potential significance the disease. In this context, we aim to shed light on involvement disease, by determining albumin quotient (QAlb) at time of diagnosis ALS a large cohort patients. Patients from university hospital Tours (n = 307) were included monocentric, retrospective study. total, 92 patients (30%) had elevated QAlb levels. This percentage was higher males (43%) than females (15%). Interestingly, not associated with age onset, sampling or diagnostic delay. However, found an association functional rating scale-revised (ALSFRS-r) but significant only males. The levels linked presence pathogenic mutation. Finally, performed multivariate survival analysis and that significantly male (HR 2.3, 95% CI 1.2-4.3, p 0.009). A longitudinal evaluation markers impairment, combination inflammatory biomarkers, could give insight into CNS pathogenesis gender difference might guide development new drugs help personalise treatment ALS.

Язык: Английский

The contribution of the peripheral immune system to neurodegeneration DOI
Huilin Li, Christian S. Lobsiger, Séverine Boillée

и другие.

Nature Neuroscience, Год журнала: 2023, Номер 26(6), С. 942 - 954

Опубликована: Май 25, 2023

Язык: Английский

Процитировано

50
Fluid biomarkers for amyotrophic lateral sclerosis: a review DOI Creative Commons
Katherine E. Irwin, Udit Sheth, Philip C. Wong

и другие.

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

Опубликована: Янв. 24, 2024

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. Presently, three FDA-approved drugs are available to help slow functional decline for patients with ALS, but no cure yet exists. With an average life expectancy only two five years after diagnosis, there clear need biomarkers improve care ALS expedite treatment development. Here, we provide review efforts made towards identifying diagnostic, prognostic, susceptibility/risk, response fluid intent facilitate more rapid accurate better predict prognosis, clinical trial design, inform interpretation results. Over course 20 + years, several promising biomarker candidates have emerged. These will be discussed, as exciting new strategies being explored discovery

Язык: Английский

Процитировано

28
Pesticides at brain borders: Impact on the blood-brain barrier, neuroinflammation, and neurological risk trajectories DOI
Noémie Cresto,

Isabel Forner-Piquer,

Asma Baig

и другие.

Chemosphere, Год журнала: 2023, Номер 324, С. 138251 - 138251

Опубликована: Март 4, 2023

Язык: Английский

Процитировано

35
Multiomics and machine-learning identify novel transcriptional and mutational signatures in amyotrophic lateral sclerosis DOI Creative Commons
Alberto Catanese, Sandeep Rajkumar, Doron D. Sommer

и другие.

Brain, Год журнала: 2023, Номер 146(9), С. 3770 - 3782

Опубликована: Март 6, 2023

Abstract Amyotrophic lateral sclerosis is a fatal and incurable neurodegenerative disease that mainly affects the neurons of motor system. Despite increasing understanding its genetic components, their biological meanings are still poorly understood. Indeed, it not clear to which extent pathological features associated with amyotrophic commonly shared by different genes causally linked this disorder. To address point, we combined multiomics analysis covering transcriptional, epigenetic mutational aspects heterogenous human induced pluripotent stem cell-derived C9orf72-, TARDBP-, SOD1- FUS-mutant as well datasets from patients’ biopsies. We identified common signature, converging towards increased stress synaptic abnormalities, reflects unifying transcriptional program in despite specific profiles due underlying pathogenic gene. In addition, whole genome bisulphite sequencing altered gene expression observed mutant cells methylation profile, highlighting deep alterations part abnormal signatures sclerosis. then applied multi-layer machine-learning integrate publicly available blood spinal cord transcriptomes found statistically significant correlation between top predictor sets, were significantly enriched toll-like receptor signalling. Notably, overrepresentation term also correlated signature neurons, novel insights into marker tissue-independent manner. Finally, using combination learning, generated first for defined genomic profile disease, ageing signatures, hinting at age major player This work describes innovative methodological approaches identification through provides knowledge on convergencies defining

Язык: Английский

Процитировано

25
Crosstalk between Oxidative Stress and Inflammation Caused by Noise and Air Pollution—Implications for Neurodegenerative Diseases DOI Creative Commons
Marin Kuntić, Omar Hahad,

Thomas Münzel

и другие.

Antioxidants, Год журнала: 2024, Номер 13(3), С. 266 - 266

Опубликована: Фев. 22, 2024

Neurodegenerative diseases are often referred to as of old age, and with the aging population, they gaining scientific medical interest. Environmental stressors, most notably traffic noise air pollution, have recently come forefront, emerged disease risk factors. The evidence for a connection between environmental factors neurodegenerative is growing. In this review, common their epidemiological association pollution presented. Also, important mechanisms involved in development, oxidative stress, neuroinflammation highlighted. An overview vivo findings will provide mechanistic link noise, pathology. Finally, importance direct indirect pathways, by which cause cerebral damage, discussed. More high-quality data still needed from both basic science studies order better understand causal

Язык: Английский

Процитировано

13
Cerebrospinal fluid and blood exosomes as biomarkers for amyotrophic lateral sclerosis; a systematic review DOI Creative Commons
Shahram Darabi,

Armin Ariaei,

Auob Rustamzadeh

и другие.

Diagnostic Pathology, Год журнала: 2024, Номер 19(1)

Опубликована: Март 1, 2024

Abstract Background Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis monitoring disease progression, today’s diagnoses are based on ruling out other diseases, neurography, electromyography examination, which takes time-consuming procedure. Methods PubMed, ScienceDirect, Web of Science were explored extract articles published from January 2015 June 2023. In searching strategy following keywords included; amyotrophic sclerosis, biomarkers, cerebrospinal fluid, serum, plama. Results A total number 6 studies describing fluid-based exosomal included this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, FUS could be detected microvesicles (MVs). Moreover, TDP-43 NFL extracted plasma exosomes used as prognostic biomarkers. Also, downregulated miR-27a-3p through exoEasy Maxi exoQuick Kit measured diagnostic biomarker. Eventually, upregulated level CORO1A monitor progression. Conclusion Based results, each biomarker alone insufficient evaluate ALS. CNS-derived contain multiple ALS-related (SOD1, FUS, miRNAs) detectable fluid blood proper alternation. Exosome detecting kits listed exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, Exo-Flow, helpful reach purpose.

Язык: Английский

Процитировано

9
Probiotics and microbial metabolites maintain barrier and neuromuscular functions and clean protein aggregation to delay disease progression in TDP43 mutation mice DOI Creative Commons
Yongguo Zhang, Yinglin Xia, Jun Sun

и другие.

Gut Microbes, Год журнала: 2024, Номер 16(1)

Опубликована: Июнь 11, 2024

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease. The ALS mice expressing human mutant of transactive response DNA binding protein 43 kDa (hmTDP43) showed intestinal dysfunction before symptoms. We hypothesize that restoring the and microbial homeostasis with bacterial metabolite or probiotics delays disease onset. investigate pathophysiological changes in intestine neurons, blood–brain barriers, inflammation during progression. then cultured enteric glial cells (EGCs) isolated from TDP43 for mechanistic studies. had significantly decreased mobility, increased permeability, weakened muscle, compared age-matched wild-type mice. observed hmTDP43 Glial fibrillary acidic (GFAP), expression α-smooth muscle actin (α-SMA), tight junction proteins (ZO-1 Claudin-5) colon, spinal cord, brain reduced Butyryl-coenzyme A CoA transferase, butyrate-producing bacteria Butyrivibrio fibrisolvens, Bacteroides fragilis, to WT Serum cytokines (IL-6, IL-17, IFN-γ) LPS were elevated EGCs aggregation associated GFAP ionized calcium-binding adaptor molecule (IBA1, microglia marker). treated butyrate probiotic VSL#3 rotarod time, mobility untreated group. Butyrate treatment GFAP, TDP43, α-SMA, ZO-1, Claudin-5 brain. Also, enhanced inflammatory IBA1, aggregation. Restoring by beneficial metabolites provide potential therapeutic strategy treat ALS.

Язык: Английский

Процитировано

8
Amyotrophic Lateral Sclerosis: Insights and New Prospects in Disease Pathophysiology, Biomarkers and Therapies DOI Creative Commons
Jameel M. Al-Khayri, Mithunan Ravindran, Akshatha Banadka

и другие.

Pharmaceuticals, Год журнала: 2024, Номер 17(10), С. 1391 - 1391

Опубликована: Окт. 18, 2024

Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disorder marked by the gradual loss of motor neurons, leading to significant disability and eventual death. Despite ongoing research, there are still limited treatment options, underscoring need for deeper understanding disease’s complex mechanisms identification new therapeutic targets. This review provides thorough examination ALS, covering its epidemiology, pathology, clinical features. It investigates key molecular mechanisms, such as protein aggregation, neuroinflammation, oxidative stress, excitotoxicity that contribute neuron degeneration. The role biomarkers highlighted their importance in early diagnosis disease monitoring. Additionally, explores emerging approaches, including inhibitors neuroinflammation modulators, antioxidant therapies, gene therapy, stem cell-based treatments. advantages challenges these strategies discussed, with an emphasis on potential precision medicine tailor treatments individual patient needs. Overall, this aims provide comprehensive overview current state ALS research suggest future directions developing effective therapies.

Язык: Английский

Процитировано

7
Physiological and pathological consequences of exosomes at the blood–brain-barrier interface DOI Creative Commons

Leila Salimi,

Fatemehsadat Seyedaghamiri,

Mohammad Karimipour

и другие.

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Май 19, 2023

Abstract Blood–brain barrier (BBB) interface with multicellular structure controls strictly the entry of varied circulating macromolecules from blood-facing surface into brain parenchyma. Under several pathological conditions within central nervous system, integrity BBB is disrupted due to abnormal crosstalk between cellular constituents and recruitment inflammatory cells. Exosomes (Exos) are nano-sized extracellular vesicles diverse therapeutic outcomes. These particles transfer a plethora signaling molecules potential modulate target cell behavior in paracrine manner. Here, current review article, properties Exos their alleviation compromised were discussed.

Язык: Английский

Процитировано

13
The Inflammatory Puzzle: Piecing together the Links between Neuroinflammation and Amyotrophic Lateral Sclerosis DOI Creative Commons
Di He, Yan Xu, Mingsheng Liu

и другие.

Aging and Disease, Год журнала: 2023, Номер 15(1), С. 96 - 96

Опубликована: Май 23, 2023

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that has complex genetic basis. Through advancements in screening, researchers have identified more than 40 mutant genes associated with ALS, some of which impact immune function. Neuroinflammation, abnormal activation cells and excessive production inflammatory cytokines the central nervous system, significantly contributes to pathophysiology ALS. In this review, we examine recent evidence on involvement ALS-associated dysregulation, specific focus cyclic GMP-AMP synthase (cGAS)-stimulator interferon (STING) signaling pathway N6-methyladenosine (m

Язык: Английский

Процитировано

13