Loyola University Chicago Molecular Pharmacology & Neuroscience

27/07/2020

A postmortem study conducted by the Sodhi Lab at the Department of Molecular Pharmacology and Neuroscience reveals that depressed females, but not males, may have higher expression of neuronal glutamate transporters in the dorsolateral prefrontal cortex in the brain. Glial glutamate transporters in the same brain region have lower expression in depressed females who died by su***de and in depressed males who chose violent methods of su***de. These data indicate that excess glutamate in the synapse due to abnormal transcriptional regulation of glutamate transporters may result in dysfunction of the dorsolateral prefrontal cortex in patients with depression, perhaps leading to impaired problem solving skills and poor decision making. These data add to the growing body of research revealing that the glutamate system contributes to the pathological mechanisms leading to depression and su***de. Moreover, glutamate transporters may be novel targets for the development of more efficacious antidepressant drugs.

Powers BE, Joyce C, Kleinman JE, Hyde TM, Ajilore O, Leow A and *Sodhi MS (2020). S*x differences in the transcription of glutamate transporters in major depression and su***de. https://doi.org/10.1016/j.jad.2020.07.055

10/01/2020

On January 8, 2020 - Loyola University Chicago - Department of Pharmacology and Neuroscience welcomes Dr. Raghu Krishnamoorthy, Ph.D., UNT Health Science Center, Fort Worth, Texas for his presentation "Endothelin-mediated neurodegeneration and strategies for neuroprotection in glaucoma".

05/04/2019

27/07/2018

The Bakowska Laboratory is proud to announce that they have published the following paper in Biochemical and Biophysical Research Communications, “PB1 and UBA domains of p62 are essential for aggresome-like induced structure formation.” (https://www.ncbi.nlm.nih.gov/pubmed/29966650)

Abstract of the paper

Aggresome-like induced structure (ALIS) are large, transient, cytosolic aggregates that serve as storage compartments for ubiquitin-tagged defective ribosomal products. We determined the importance of the protein p62 in the formation of ALIS and demonstrated that two domains of p62-PB1 and UBA-are essential for ALIS assembly. Those two major binding domains of p62, also known as sequestosome 1, were shown to play a critical role in the formation of autophagosomes or cytoplasmic aggregates. Specifically, the PB1 domain is essential for self-oligomerization, and the UBA domain allows p62 to bind to polyubiquitin chains or ubiquitinated proteins. After stimulation of RAW 264.7 macrophages with lipopolysaccharide, we observed a significant decrease in the number of cells with ALIS. Importantly, cells overexpressing either a PB1 mutant or UBA-deleted p62 construct also exhibited a substantially diminished number of cells containing ALIS. Since both p62 and ubiquitin are found in ALIS, we evaluated the dynamics of YFP-tagged p62 in ALIS using fluorescence recovery after photobleaching (FRAP). In contrast to the findings of a previous study that showed high GFP-tagged ubiquitin motility in ALIS, we determined that YFP-tagged p62 has very limited mobility (see Figure below). Lastly, we determined that GST-tagged full-length p62 binds to Lys-63-linked polyubiquitin chains but not to Lys-48-linked chains. Overall, our findings provide insight on the essential role that p62, particularly its PB1 and UBA domains, has in the formation of ALIS.

Biochem Biophys Res Commun. 2018 Jul 2. pii: S0006-291X(18)31472-4. doi: 10.1016/j.bbrc.2018.06.153. [Epub ahead of print]

27/07/2018