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Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase-dependent mechanism

1 year 10 months ago
The Parkinson's disease (PD)-linked protein Leucine-Rich Repeat Kinase 2 (LRRK2) consists of seven domains, including a kinase and a Roc G domain. Despite the availability of several high-resolution structures, the dynamic regulation of its unique intramolecular domain stack is nevertheless still not well understood. By in-depth biochemical analysis, assessing the Michaelis-Menten kinetics of the Roc G domain, we have confirmed that LRRK2 has, similar to other Roco protein family members, a K(M)...
Bernd K Gilsbach

A subset of human dermal fibroblasts overexpressing Cockayne syndrome group B protein resist UVB radiation-mediated premature senescence

1 year 10 months ago
Ultraviolet B (UVB) radiation is a major contributor to skin photoaging. Although mainly absorbed by the epidermis, UVB photons managing to penetrate the upper dermis affect human dermal fibroblasts (HDFs), leading, among others, to the accumulation of senescent cells. In vitro studies have shown that repeated exposures to subcytotoxic UVB radiation doses provoke HDFs' premature senescence shortly after the end of the treatment period. Here, we found that repetitive exposures to non-cytotoxic...
Asimina Fotopoulou

Dynamic mitophagy trajectories hallmark brain aging

1 year 10 months ago
Studies using mitophagy reporter mice have established steady-state landscapes of mitochondrial destruction in mammalian tissues, sparking intense interest in basal mitophagy. Yet how basal mitophagy is modified by healthy aging in diverse brain cell types has remained a mystery. We present a comprehensive spatiotemporal analysis of mitophagy and macroautophagy dynamics in the aging mammalian brain, reporting critical region- and cell-specific turnover trajectories in a longitudinal study. We...
Anna Rappe

Age-Dependent Bi-Phasic Dynamics of Ly49<sup>+</sup>CD8<sup>+</sup> Regulatory T Cell Population

1 year 10 months ago
Aging is tightly associated with reduced immune protection but increased risk of autoimmunity and inflammatory conditions. Regulatory T cells are one of the key cells to maintaining immune homeostasis. The age-dependent changes in CD4^(+)Foxp3^(+) regulatory T cells (Tregs) have been well documented. However, the nonredundant Foxp3^(-)CD8^(+) Tregs were never examined in the context of aging. This study first established clear distinctions between phenotypically overlapping CD8^(+) Tregs and...
Saranya Srinivasan