Опубликована: Янв. 1, 2024
Язык: Английский
Ageing Research Reviews, Год журнала: 2024, Номер unknown, С. 102642 - 102642
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
4
PLoS Biology, Год журнала: 2025, Номер 23(2), С. e3002974 - e3002974
Опубликована: Фев. 18, 2025
Parkinson’s disease (PD) is a neurodegenerative characterized by the death of dopaminergic neurons in substantia nigra and formation Lewy bodies that are composed aggregated α-synuclein (α-Syn). However, factors regulate α-Syn pathology nigrostriatal degeneration remain poorly understood. Previous studies demonstrate cholesterol 24-hydroxylase (CYP46A1) increases risk for PD. Moreover, 24-hydroxycholesterol (24-OHC), brain-specific oxysterol catalyzed CYP46A1, elevated cerebrospinal fluid PD patients. Herein, we show levels CYP46A1 24-OHC patients increase with age mouse model. Overexpression intensifies pathology, whereas genetic removal attenuates neurotoxicity brain. supplementation exogenous exacerbates mitochondrial dysfunction induced fibrils. Intracerebral injection enhances spread neurodegeneration via X-box binding protein 1 (XBP1) lymphocyte-activation gene 3 (LAG3) levels. Thus, promote XBP1–LAG3 axis. Strategies aimed at inhibiting CYP46A1-24-OHC axis LAG3 could hold promise as disease-modifying therapies
Язык: Английский
Процитировано
0
Research Square (Research Square), Год журнала: 2025, Номер unknown
Опубликована: Март 17, 2025
Hyperhomocysteinemia (HHcy)-inducing diets recapitulate small cerebral vessel disease phenotypes in mice including cerebrovascular pathology/dysfunction, neuroinflammation, synaptic deficits, and cognitive decline. We recently showed that astrocyte signaling through calcineurin(CN)/nuclear factor of activated T cells (NFATs) plays a causative role these phenotypes. Here, we assessed the impact astrocytic on microglia, which set inflammatory tone brain. Seven-to-eight-week-old male female C57BL/6J received intrahippocampal injections AAV2/5-Gfa2-EGFP (control) or adeno-associated virus (AAV) expressing NFAT inhibitor VIVIT ( i.e. , AAV2/5-Gfa2-VIVIT-EGFP). Mice were then fed with control chow (CT) B-vitamin-deficient for 12 weeks to induce HHcy. Immunohistochemistry was used assess expression pan-microglial marker Iba1 homeostatic microglial P2ry12. little sensitivity diet, AAV treatment, sex. Conversely, P2ry12 reduced HHcy diet males, but not females. Treatment males AAV-Gfa2-VIVIT prevented loss next conducted single-cell RNA sequencing (scRNAseq) determine if genes and/or clustering patterns sensitive sex-dependent manner. In disease-associated subclusters overrepresented HHcy-treated mice, while promoted appearance clusters. contrast, females less treatments, though disease-like gene also observed condition. However, very few HHcy-sensitive affected by VIVIT. The results suggest sexually dimorphic influence context disease.
Язык: Английский
Процитировано
0
Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(3), С. 200 - 200
Опубликована: Март 18, 2025
The rising prevalence of Alzheimer’s disease (AD), particularly among older adults, has driven increased research into its underlying mechanisms and risk factors. Aging, genetic susceptibility, cardiovascular health are recognized contributors to AD, but how the age onset affects progression remains underexplored. This study investigates role early- versus late-onset (EOAD LOAD, respectively) in shaping trajectory cognitive decline. Leveraging data from Religious Orders Study Memory Aging Project (ROSMAP), two cohorts were established: individuals with early-onset AD those AD. Comprehensive analyses, including differential gene expression profiling, pathway enrichment, co-expression network construction, conducted identify distinct molecular signatures associated each cohort. Network modularity learning algorithms used discern inner structure networks their related functional features. Computed descriptors provided deeper insights influence at on biological
Язык: Английский
Процитировано
0
Neuroscience, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
EMBO Reports, Год журнала: 2025, Номер unknown
Опубликована: Апрель 30, 2025
After peripheral nerve injury, the structure of spinal cord is actively regulated by glial cells, contributing to chronicity neuropathic pain. However, mechanism which injury leads synaptic imbalance remains elusive. Here, we use a pH-reporter system and find that triggers reorganization excitatory synapses influenced accumulation ganglioside GT1b at afferent terminals. acts as protective signal against injury-induced synapse elimination. Inhibition GT1b-synthesis increases phagocytosis pre-synapses reduces post-injury. In vitro analyses reveal positive correlation between frequency pre-synaptic calcium activity, with GT1b-mediated suppression occurring through SYK dephosphorylation. Our study highlights GT1b's pivotal role in preventing elimination after offers new insight into molecular underpinning activity-dependent stability phagocytosis.
Язык: Английский
Процитировано
0
Cells, Год журнала: 2024, Номер 13(17), С. 1426 - 1426
Опубликована: Авг. 26, 2024
There is an urgent need for effective disease-modifying therapeutic interventions Alzheimer's disease (AD)-the most prevalent cause of dementia with a profound socioeconomic burden. Most clinical trials targeting the classical hallmarks this disease-β-amyloid plaques and neurofibrillary tangles-failed, showed discrete effects, or were accompanied by concerning side effects. has been ongoing search novel targets. Neuroinflammation, now widely recognized as hallmark all neurodegenerative diseases, proven to be major contributor AD pathology. Here, we summarize role neuroinflammation in pathogenesis progression discuss potential targets such microglia, TREM2, complement system, inflammasomes, cytosolic DNA sensors. We also present overview studies specific innate immune system components, highlighting progress field drug research while bringing attention delicate nature modulations AD.
Язык: Английский
Процитировано
2
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9573 - 9573
Опубликована: Сен. 4, 2024
Alzheimer’s disease (AD) represents a significant global health challenge and affects approximately 50 million people worldwide. This overview of published reviews provides comprehensive understanding the intricate correlations between AD body composition, focusing particularly on obesity. We used systematic approach to collect analyze relevant topic obesity disease. A search electronic databases, including PubMed, MEDLINE, Google Scholar, was conducted. searched keywords such as “Alzheimer’s disease”, “body composition”, “lean mass”, “bone “fat mass”. considered only written within past 5 years in English. Fifty-six were identified that shed light multiple connections composition. The review involves several aspects, impact lean mass, bone endocrinological factors related obesity, well inflammation, neuroinflammation, molecular/genetic factors. findings highlight complex interplay these elements development AD, underscoring need for holistic approaches reduce risk explore innovative strategies diagnosis, prevention, treatment.
Язык: Английский
Процитировано
1
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Июнь 10, 2024
Abstract Many neurodegenerative disorders (NDDs) preferentially affect neurons with long or complex axonal arbors, but our understanding of this specific vulnerability is limited. Using Drosophila larval class IV dendrite arborization (C4da) neurons, we found that neuronal activation the integrated stress response (ISR) induces axon length-dependent degeneration (LDD). We identified Interleukin-6 homologue unpaired 3 (upd3) as both necessary and sufficient for LDD in C4da neurons. Upd3 recruits glial cells to phagocytose presynapses on axons, revealing an intrinsic glia-mediated presynapse removal. Finally, loss fly models human NDDs utilized pathway. Altogether, studies identify inflammatory cytokine signaling from glia a key determinant vulnerability. One-Sentence Summary Sensory exhibit removal driven by glia.
Язык: Английский
Процитировано
0
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0