CD33 and clusterin interact biophysically and genetically to modulate Alzheimer risk.

We report the results of structural, functional and genetic studies on the CD33 sialic acid- binding receptor that reveal how non-coding variants in CD33 alter risk for Alzheimer's disease (AD). The full-length CD33 isoform, whose expression is upregulated by non-coding AD-risk alleles, preferentially forms dimers at the cell surface, where they interact with AD-related proteins (clusterin and Aβ). This interaction induces CD33 inhibitory signalling and downregulates protective microglial functions including phagocytic removal of amyloid plaques.

CD33-CD45 Interaction Reveals a Mechanistic Link to Alzheimer's Disease Susceptibility.

The innate immune gene 33, encoding a myeloid inhibitory sialic acid-binding receptor, is associated with Alzheimer's disease (AD) susceptibility. The AD-associated risk variant reduces splicing of the sialic acid-binding domain and increases expression of the full-length (sialic acid-binding) CD33 isoform seven-fold compared to the protective genotype. Here we identify CD45 as an immune cell-specific sialic acid-dependent CD33 binding partner, whose phosphatase activity is inhibited by CD33.

Altered mitochondria-associated ER membrane (MAM) function shifts mitochondrial metabolism in amyotrophic lateral sclerosis (ALS).

Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here that this impairment in the crosstalk between mitochondria and the ER impedes the use of glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids to sustain energy production.

CD33 and SHP-1/ Interaction in Alzheimer's Disease.

Large-scale genetic studies have identified numerous genetic risk factors that suggest a central role for innate immune cells in susceptibility to Alzheimer's disease (AD). CD33, an immunomodulatory transmembrane sialic acid binding protein expressed on myeloid cells, was identified as one such genetic risk factor associated with Alzheimer's disease. Several studies explored the molecular outcomes of genetic variation at the locus.

Size-frequency distributions and physical properties of chondrules from x-ray computed microtomography and digital data extraction.

Within this work, we present the first true three-dimensional (3D) analysis of chondrule size. Knowledge about the physical properties of chondrules is important for validating astrophysical theories concerning chondrule formation and their aggregation into the chondritic meteorites (known as chondrites) that contain them. The classification of chondrites into chemical groups also relies on chondrule properties, including their dimensions.

Assessing mitochondrial respiratory bioenergetics in whole cells and isolated organelles by microplate respirometry.

Mitochondria are responsible for the generation of ATP by oxidative phosphorylation; however, these multifaceted organelles regulate many other key cellular functions as well, such as calcium homeostasis, apoptosis, and biosynthesis of steroid hormones, heme and phospholipids. In order to carry out these functions, mitochondria establish physical and functional connections with other organelles such as the plasma membrane, lipid droplets/vesicles, peroxisomes, endosomes, and the endoplasmic reticulum. Dysregulation of any of the aforementioned processes or inter-organelle contacts can lead to mitochondrial dysfunction and subsequent changes in oxygen consumption and ATP production.

The dark side of browning.

The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning.