Environment International, Год журнала: 2024, Номер 194, С. 109151 - 109151
Опубликована: Ноя. 16, 2024
Язык: Английский
npj Parkinson s Disease, Год журнала: 2025, Номер 11(1)
Опубликована: Янв. 8, 2025
Abstract The risk of Parkinson’s disease (PD) associated with farming has received considerable attention, in particular for pesticide exposure. However, data on PD specific activities is lacking. We aimed to explore whether exhibited a higher than others among the entire French farm manager (FM) population. A secondary analysis real-world administrative insurance claim and electronic health/medical records (TRACTOR project) was conducted estimate 26 using mining. cases were identified through chronic declarations antiparkinsonian drug claims. There 8845 1,088,561 FMs. highest-risk group included FMs engaged pig farming, cattle truck fruit arboriculture, crop mean hazard ratios (HRs) ranging from 1.22 1.67. lowest-risk all involving horses small animals, as well gardening, landscaping reforestation companies (mean HRs: 0.48–0.81). Our findings represent preliminary work that suggests potential involvement occupational factors related onset development. Future research focusing farmers high-risk will allow uncover by better characterizing exposome, which could improve surveillance farmers.
Язык: Английский
Процитировано
2
Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)
Опубликована: Март 3, 2025
Abstract Alzheimer’s disease (AD) is the most common neurodegenerative worldwide. Amyloid-β (Aβ) accumulation and neurofibrillary tangles are two key histological features resulting in progressive irreversible neuronal loss cognitive decline. The macrophages of central nervous system (CNS) belong to innate immune comprise parenchymal microglia CNS-associated (CAMs) at CNS interfaces (leptomeninges, perivascular space choroid plexus). Microglia CAMs have received attention as they may play a role onset progression e. g., by clearing amyloid beta through phagocytosis. Genome-wide association studies (GWAS) revealed that human express numerous risk genes for AD, further highlighting their potentially critical AD pathogenesis. tightly controlled environmental factors, such host microbiota. Notably, it was reported composition gut microbiota differed between patients healthy individuals. Hence, emerging analyzed impact bacteria different preclinical mouse models well clinical studies, enabling promising new therapeutic options.
Язык: Английский
Процитировано
1
Movement Disorders, Год журнала: 2024, Номер 39(10), С. 1710 - 1715
Опубликована: Сен. 9, 2024
Язык: Английский
Процитировано
8
Brain Sciences, Год журнала: 2024, Номер 14(5), С. 471 - 471
Опубликована: Май 7, 2024
Plastic production, which exceeds one million tons per year, is of global concern. The constituent low-density polymers enable spread over large distances and micro/nano particles (MNPLs) induce organ toxicity via digestion, inhalation, skin contact. Particles have been documented in all human tissues including breast milk. MNPLs, especially weathered particles, can breach the blood–brain barrier, inducing neurotoxicity. This has non-human species, human-induced pluripotent stem cell lines. Within brain, MNPLs initiate an inflammatory response with pro-inflammatory cytokine oxidative stress generation reactive oxygen mitochondrial dysfunction. Glutamate GABA neurotransmitter dysfunction also ensues alteration excitatory/inhibitory balance favor reduced inhibition resultant neuro-excitation. Inflammation cortical hyperexcitability are key abnormalities involved pathogenic cascade amyotrophic lateral sclerosis (ALS) intricately related to mislocalization aggregation TDP-43, a hallmark ALS. Water many foods contain humans, ingestion main form exposure. Digestion plastics within gut alter their properties, rendering them more toxic, they cause microbiome dysbiosis dysfunctional gut–brain axis. recognized as trigger and/or aggravating factor for ALS associated long (years or decades) preclinical period neonates infants exposed through milk, milk substitutes, toys. endangers time intense neurogenesis establishment neuronal circuitry, setting stage development neurodegeneration later life. MNPL neurotoxicity should be considered yet unrecognized risk diseases.
Язык: Английский
Процитировано
7
Human Genomics, Год журнала: 2025, Номер 19(1)
Опубликована: Апрель 30, 2025
Understanding the interplay between genetic predisposition and environmental lifestyle exposures is essential for advancing precision medicine public health. The exposome, defined as sum of all an individual encounters throughout their lifetime, complements genomic data by elucidating how external internal exposure factors influence health outcomes. This treatise highlights emerging discipline translational exposomics that integrates genomics, offering a comprehensive approach to decipher complex relationships exposures, variability, disease phenotypes. We highlight cutting-edge methodologies, including multi-omics technologies, exposome-wide association studies (EWAS), physiology-based biokinetic modeling, advanced bioinformatics approaches. These tools enable precise characterization both facilitating identification biomarkers, exposure-response relationships, prediction mechanisms. also consider importance addressing socio-economic, demographic, gender disparities in research. emphasize exposome can contextualize variation enhance causal inference, especially vulnerable populations diseases. By showcasing concrete examples proposing integrative platforms exposomics, this work underscores critical need bridge genomics prevention, risk stratification, decision-making. offers new paradigm understanding beyond genetics alone.
Язык: Английский
Процитировано
1
Muscle & Nerve, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 7, 2024
Several decades have passed since the anterograde corticomotoneuronal hypothesis for amyotrophic lateral sclerosis (ALS) was proposed. The intervening years witnessed its emergent support based on anatomical, pathological, physiological, neuroimaging, and molecular biological studies. evolution of an extensive system appears restricted to human species, with ALS representing a uniquely disease. While some, very select non-human primates limited projections, these tend be absent in all other animals. From general perspective, early clinical features may considered reflect failure system. characteristic loss skilled motor dexterity involving limbs, speech impairment through progressive bulbar dysfunction specifically involve those units having strongest projections. A similar explanation likely underlies unique "split phenotypes" that now been well characterized ALS. Large Betz cells pyramidal projecting neurons, their dendritic arborization, are particularly vulnerable elements exposome such as aging, environmental stress lifestyle changes. Progressive proteosome impairs nucleocytoplasmic shuffling induces toxic but soluble TDP-43 aggregate corticomotoneurons. cell is further accentuated profuse arborizations. Clarification specific genomes neural networks will promote initiation precision medicine approaches directed key structure neurological manifestations ALS,
Язык: Английский
Процитировано
6
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7221 - 7221
Опубликована: Июнь 29, 2024
Decades of research have identified genetic and environmental factors involved in age-related neurodegenerative diseases and, to a lesser extent, neuropsychiatric disorders. Genomic instability, i.e., the loss genome integrity, is common feature among both (mayo-trophic lateral sclerosis, Parkinson's disease, Alzheimer's disease) psychiatric (schizophrenia, autism, bipolar depression) instability associated with accumulation persistent DNA damage activation response (DDR) pathways, as well pathologic neuronal cell or senescence. Typically, DDR signaling ensures that genomic proteomic homeostasis are maintained dividing cells, including neural progenitors, post-mitotic neurons. However, dysregulation these protective responses, part due aging insults, contributes progressive development and/or In this Special Issue, we introduce highlight overlap between disorders, emerging clinical, genomic, molecular evidence for contributions aberrant repair. Our goal illuminate importance subject uncover possible treatment prevention strategies relevant devastating brain diseases.
Язык: Английский
Процитировано
4
Journal of Parkinson s Disease, Год журнала: 2024, Номер unknown, С. 1 - 29
Опубликована: Сен. 25, 2024
Increasing evidence suggests a potential role for infectious pathogens in the etiology of synucleinopathies, group age-related neurodegenerative disorders including Parkinson’s disease (PD), multiple system atrophy and dementia with Lewy bodies. In this review, we discuss link between infections synucleinopathies from historical perspective, present emerging that supports link, address current research challenges focus on neuroinflammation. Infectious can elicit neuroinflammatory response modulate genetic risk PD related synucleinopathies. The mechanisms how might be linked as well overlap immune cellular pathways affected by virulent disease-related factors are discussed. Here, an important α-synuclein against is emerging. Critical methodological knowledge gaps addressed, provide new future perspectives to these gaps. Understanding neuroinflammation influence will essential development early diagnostic tools novel therapies.
Язык: Английский
Процитировано
3
Journal of Neurology, Год журнала: 2025, Номер 272(4)
Опубликована: Апрель 1, 2025
Язык: Английский
Процитировано
0
Alzheimer s & Dementia, Год журнала: 2025, Номер 21(5)
Опубликована: Май 1, 2025
Abstract Per‐ and polyfluoroalkyl substances (PFAS) are ubiquitous persistent organic pollutants. The neurotoxic cardiometabolic effects of PFAS well documented, leading to the hypothesis that exposure increases dementia risk. However, empirical data on in relation cognitive impairment weak, limited, inconsistent. This report reviews literature provides a rationale overview VascCog Longitudinal Study, new study using population‐based Northern Manhattan Study cohort, prospectively examine serum concentrations 13 lipids, carotid atherosclerosis, impairment, dementia. We hypothesize deleteriously impact cognition through pathway involving hyperlipidemia atherosclerosis. Rigorous examination is needed inform public health policies PFAS‐containing products, support regulations reduce community exposure, provide avenues protect at individual levels. Highlights risk factors neurotoxicity. Data controversial. mechanistic can policy.
Язык: Английский
Процитировано
0