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Restoration of striatal neuroprotective pathways by kinase inhibitor treatment of Parkinson's disease-linked LRRK2-mutant mice
Parkinson's disease is associated with activating mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2), which suppresses primary cilia formation in cholinergic and parvalbumin interneurons and astrocytes in the striatum. As a result, there is a decrease in the production of neuroprotective glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), which normally support the viability of dopaminergic neurons. MLi-2 is a brain-penetrant, selective, and now experimental...
Association between self-reported multimorbidity and longitudinal brain Abeta deposition in Alzheimer's disease
Multimorbidity is common in older adults. However, whether multimorbidity accelerates brain beta-amyloid (Aβ) deposition, the molecular driver of Alzheimer's disease (AD), in humans remains largely unknown. In this study, we selected 435 brain Aβ-positive participants with available longitudinal Aβ-PET data (mean duration 3.9 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Twenty-two self-reported chronic disorders were considered as a measure of the severity of...
Integrated dopamine sensing and 40 Hz hippocampal stimulation improves cognitive performance in Alzheimer's mouse models
Hippocampal degeneration and reduced dopamine levels in Alzheimer's disease are associated with severe memory and cognitive impairments. However, the lack of multifunctional in situ neural chips has posed challenges for integrated investigations of Alzheimer's disease pathophysiology, dopamine dynamics, and neural activity. Therefore, we developed NeuroRevive-FlexChip, a flexible neural interface capable of precise electrical modulation and simultaneous in situ monitoring of dopamine levels and...
Bridging expectations and science: a roadmap for the future of longevity interventions
The field of longevity interventions has witnessed rapid expansion, driven by scientific advancements alongside growing industry and consumer interest. However, no longevity intervention has yet been proven effective or ready for widespread clinical adoption. A substantial gap persists between public expectations and the current scientific realities. This article explores four key themes: (1) consumer priorities regarding longevity interventions, (2) the type and depth of scientific information...
The combination of hawthorn extract administration and high-intensity interval training (HIIT) alleviates hippocampus damage in aged rats: the behavioral, molecular and histological evaluations
The aging process results in a gradual decline in brain function, characterized by heightened hippocampal atrophy and dysfunction. Physical activity can enhance cognitive skills in elderly individuals and is significant in the prevention of neurodegenerative illnesses. Hawthorn (Crataegus oxyacantha) is a fruit-bearing shrub with a longstanding history as a medicinal agent. Currently, hawthorn is predominantly utilized for a range of pathological diseases. This research is designed to assess the...
Identification of Functional Cellular Markers Related to Human Health, Frailty and Chronological Age
Aging leads to a decline in physiological reserves, an increase in age-related diseases, reduced functional ability and a shortened healthspan. While molecular markers of chronological aging exist, their link to general health and intrinsic capacity (IC), a composite measure of physical and mental capacities, remains unclear. This study integrates the WHO's Healthy Aging framework with geroscience to explore fibroblasts as indicators of health. We assessed primary skin fibroblasts from 133...
Satellite glial cells: Shaping peripheral input into the brain-body axis?
Satellite glial cells (SGCs) are peripheral nervous system glial cells enveloping sensory and sympathetic ganglion neuronal soma. Traditionally viewed as mere supportive cells, recent studies reveal SGCs' dynamic role in regulating sensory and autonomic processing, positioning them to shape peripheral neural signaling. This role has the potential to impact the healthy function of numerous biological processes and contribute to disease progression. Studies now implicate peripheral sensory and...
More TOR: The expanding role of mTOR in regulating immune responses
The mammalian/mechanistic target of rapamycin (mTOR) is an evolutionarily conserved multi-node signaling pathway that integrates critical environmental cues to control cellular growth. Decades worth of studies have intricately dissected the mTOR pathway to identify regulatory signals that are essential for regulating immune cell activation, differentiation, and function. As the mTOR field continues to evolve, so too does our understanding of these new findings in immune cells. Our group and...
Leaf economic strategies drive global variation in phosphorus stimulation of terrestrial plant production
Plant biomass and its allocation are fundamental for understanding biospheric matter production. However, the impacts of atmospheric phosphorus (P) deposition on species-specific biomass and its allocation in global terrestrial plants remain unclear. By synthesizing 5548 observations of plant biomass and its allocation related to P addition worldwide, we find that P addition increases plant biomass by an average of 35% globally. This increase varies across plant functional groups, with stronger...
The Role and Mechanism of Anti-ICOS mAb in Experimental Autoimmune Encephalomyelitis
Targeting costimulatory signalling pathways, especially inducible T-cell costimulatory (ICOS)-ICOS ligand(ICOSL) co-stimulatory signal, has been widely used as a therapeutic target in autoimmune diseases. Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating and neurodegenerative disease in the central nervous system. At present, few studies are addressing the role of the ICOS-ICOSL co-stimulatory pathway in MS. We aimed to explore the role of anti-ICOS mAb in the immune response...
From hormones to neurodegeneration: how FSH drives Alzheimer's disease
The role and function of follicle-stimulating hormone in the gonads have been extremely studied. However, recent research has begun to explore the relationship between elevated follicle-stimulating hormone levels and the prevalence of extragonadal disorders, particularly in perimenopausal and postmenopausal women. These disorders include endometrial cancer, osteoporosis, obesity, and atherosclerosis. This review provides new insights into the relationship between follicle-stimulating hormone and...
CITA GO-ON study. A community based multidomain lifestyle intervention to prevent cognitive decline. Protocol design and recruitment process
INTRODUCTION: Growing research suggests that dementia is a complex disorder with multiple risk factors and causes. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated that lifestyle interventions could confer cognitive benefits. Inspired by this, the GOIZ-ZAINDU (GZ) feasibility study adapted the FINGER approach to the Basque context. Building upon the GZ study, the CITA GO-ON trial aims to enhance and expand the evidence supporting...