Enzymes and Coenzymes Commons^™

The Correlation Between A Methylenetetrahydrofolate Reductase Deficiency In Autism Spectrum Disorder Patients And The Presence Of Mental Health Disorders, Hinal Joshi, Andrea Iannuzzelli

Rowan-Virtua Research Day

• Currently little literature exists on connection between Methylenetetrahydrofolate reductase (MTHFR) deficiency and mental health disorders

• Reduced enzyme activity associated with certain MTHFR variants contributes to altered folate metabolism, elevated homocysteine levels, and disrupted DNA methylation, all of which are implicated in mental health disorders

• Identifying genetic risk factors could facilitate earlier diagnosis and intervention, leading to improved outcomes

• Relevant results could help reduce stigma and promote greater understanding of challenges faced by patients on the spectrum

A Homogeneous Time-Resolved Fluorescence Screen To Identify Sirt2 Deacetylase And Defatty-Acylase Inhibitors, Jie Yang, Joel Cassel, Brian C Boyle, Daniel Oppong, Young-Hoon Ahn, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Human sirtuin-2 (SIRT2) has emerged as an attractive drug target for a variety of diseases. The enzyme is a deacylase that can remove chemically different acyl modifications from protein lysine residues. Here, we developed a high-throughput screen based on a homogeneous time-resolved fluorescence (HTRF) binding assay to identify inhibitors of SIRT2's demyristoylase activity, which is uncommon among many ligands that only affect its deacetylase activity. From a test screen of 9600 compounds, we identified a small molecule that inhibited SIRT2's deacetylase activity (IC50 = 7 μM) as well as its demyristoylase activity (IC50 = 37 μM). The inhibitor was composed …

Janus Kinase (Jak) Inhibitors: A New Frontier In The Treatment Of Vitiligo, Catherine F. Alapatt, Amanda Greenspan, Mohammad Fardos

Rowan-Virtua Research Day

Up to 70 million people worldwide suffer from vitiligo, an autoimmune disease characterized by the destruction of melanin. Current treatment options vary in efficacy. The disease manifests clinically as white circular macules of depigmentation seen primarily on the face and appendages.1 The pathophysiology of vitiligo is multifactorial and still being studied. One proposed mechanism behind the pathophysiology of vitiligo involves the upregulation of interferon gamma (IFN-γ) with downstream effects on JAK/STAT pathways resulting in CXCL10 transcription.1,2 Here we discuss Ruxolitinib, a topical JAK inhibitor, that recently passed its clinical trial phase, and Ritlecitinib, an oral JAK inhibitor which is currently …

Effect Of Uracil Dna Glycosylase Activity On The Efficacy Of Thymidylate Synthase Inhibitor/Hdac Inhibitor Combination Therapies In Colon Cancer, Rashmi Kulkarni, Brian P Weiser

Rowan-Virtua Research Day

Human uracil DNA glycosylase (UNG2) is responsible for removing uracil bases from DNA and initiates base excision repair pathways. Accumulation of uracil or its fluorinated analogs in DNA is one of the killing mechanisms of thymidylate synthase (TS) inhibitors in cancer cells, and depletion of UNG2 often enhances the toxicity of these anticancer drugs. We tested the effect of UNG2 KO on the efficacy of multiple TS inhibitors (5-fluorouracil, fluorodeoxyuridine, and pemetrexed) and we determined that, except for 5-fluorouracil, all other TS inhibitors were significantly more potent in UNG2 KO cells compared to wild-type HT29 cells. Interestingly, UNG2 protein levels …