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Rab27b promotes lysosomal function and alpha-synuclein clearance in neurons

2 months ago
Alpha-synuclein (αsyn) is the key pathogenic protein implicated in synucleinopathies including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). In these diseases, αsyn is thought to spread between cells where it accumulates and induces pathology; however, mechanisms that drive its propagation or aggregation are poorly understood. We have previously reported that the small GTPase Rab27b is elevated in human PD and DLB and that it can mediate the autophagic clearance and toxicity of...
Kasandra Scholz

Ergothioneine controls mitochondrial function and exercise performance via direct activation of MPST

2 months ago
Ergothioneine (EGT) is a diet-derived, atypical amino acid that accumulates to high levels in human tissues. Reduced EGT levels have been linked to age-related disorders, including neurodegenerative and cardiovascular diseases, while EGT supplementation is protective in a broad range of disease and aging models. Despite these promising data, the direct and physiologically relevant molecular target of EGT has remained elusive. Here, we use a systematic approach to identify how mitochondria...
Hans-Georg Sprenger

HypoxyStat, a small-molecule form of hypoxia therapy that increases oxygen-hemoglobin affinity

2 months ago
We have previously demonstrated that chronic inhaled hypoxia is remarkably therapeutic in the premier animal model of mitochondrial Leigh syndrome, the Ndufs4 knockout (KO) mouse. Subsequent work has extended this finding to additional mitochondrial diseases and more common conditions. However, challenges inherent to gas-based therapies have hindered the rapid translation of our findings to the clinic. Here, we tested a small molecule (hereafter termed HypoxyStat) that increases the binding...
Skyler Y Blume

Regulatory Roles of Exosomes in Aging and Aging-Related Diseases

2 months ago
Exosomes are small vesicles with diameters ranging from 30 to 150 nm. They originate from cellular endocytic systems. These vesicles contain a rich payload of biomolecules, including proteins, nucleic acids, lipids, and metabolic products. Exosomes mediate intercellular communication and are key regulators of a diverse array of biological processes, such as oxidative stress and chronic inflammation. Furthermore, exosomes have been implicated in the pathogenesis of infectious diseases, autoimmune...
Nanyin Xiao