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IFNγ alters the aberrant phenotype of α-synuclein-treated microglia reducing the detrimental impact of their secretome on dopaminergic neurons

1 month 3 weeks ago
Microglia play a major role in the pathophysiology of Parkinson's disease, where they regulate both α-synuclein (αSyn) aggregate clearance and inflammatory responses. Interferon gamma (IFNγ) is a strong immunomodulator, but its role in shaping human microglial phenotypes during αSyn exposure remains incompletely understood. Further, whether the secreted factors from microglia after exposure to αSyn pre-formed fibrils (PFFs) and IFNγ can affect morphology and functionality of dopaminergic neurons...
Jonna Niskanen

Glymphatic dysfunction: a unifying hypothesis for delirium

1 month 3 weeks ago
Delirium is a common and severe neuropsychiatric syndrome with lasting cognitive consequences, yet its pathophysiology remains poorly understood. We hypothesize that impaired glymphatic flow represents a central mechanism by which delirium evolves. This hypothesis builds on recent evidence showing that major delirium risk factors, such as ageing, dementia, cardiovascular disease and renal failure, are all associated with reduced glymphatic clearance. Similarly, common delirium triggers,...
Hans Christian Boesen

Sex differences in immune responses to viruses, bacteria and vaccines

1 month 3 weeks ago
Sex differences in immune function arise from sex chromosome complement, which drives differential expression and activity of X-linked genes in immune cells, and gonadal steroids that transcriptionally regulate innate and adaptive immune cells through their respective receptors. These fundamental differences shape divergent outcomes between male and female individuals in viral and bacterial infections, post-acute infection syndromes and vaccine responses throughout the lifespan. Understanding...
Sabal Chaulagain

Targeting Mitochondrial Stress Responses: Terbinafine and Miglustat as Novel Lifespan and Healthspan Modulators

1 month 3 weeks ago
Mitochondria are central to cellular homeostasis and play a critical role in aging and age-related disorders, making them promising therapeutical targets. Here, we identify terbinafine and miglustat as novel mitochondrial stress inducers that extend lifespan and improve healthspan in Caenorhabditis elegans. Through a two-step screening, we found that both compounds activate the mitochondrial stress response (MSR) and exhibit distinct mechanisms of action. Terbinafine and miglustat robustly...
Amélia Lalou

Cytotoxic T cell recognition of α-synuclein drives pathogenic immune responses in multiple system atrophy

1 month 3 weeks ago
Multiple system atrophy (MSA) is a progressive neurologic disease, known as an α-synucleinopathy. There are currently no effective disease-modifying therapies for MSA. While neuroinflammation is a hallmark of MSA, the contribution of adaptive immune mechanisms remains poorly understood. Here, we profiled peripheral and central T cell responses in patients with MSA, in comparison with Parkinson's disease (PD) and healthy control cohorts, using single-cell transcriptomics, flow cytometry, and...
Jae-Seung Moon

Mitochondrial remodeling in skeletal muscle underlies exercise-induced reversal of age-associated functional decline in mice and humans

1 month 3 weeks ago
Loss of skeletal muscle mass and strength are common manifestations of frailty in older people and are linked to reduced quality of life. However, whether mitochondria are mechanistically linked to frailty and how physical activity, or lack thereof, is involved in age-related functional decline are still unknown. We report that exercise-induced improvements in functional capacity, including reduced frailty in old mice, are dependent on mitochondrial adaptations in skeletal muscle at structural,...
Esther García-Domínguez