Biological Screening and Crystallographic Studies of Hydroxy γ-Lactone Derivatives to Investigate PPARγ Phosphorylation Inhibition.

PPARγ represents a key target for the treatment of type 2 diabetes and metabolic syndrome. To avoid serious adverse effects related to the PPARγ agonism profile of traditional antidiabetic drugs, a new opportunity is represented by the development of molecules acting as inhibitors of PPARγ phosphorylation by the cyclin-dependent kinase 5 (CDK5). Their mechanism of action is mediated by the stabilization of the PPARγ β-sheet containing Ser273 (Ser245 in PPARγ isoform 1 nomenclature).

Neurofunctional Signature of Hyperfamiliarity for Unknown Faces.

Hyperfamiliarity for unknown faces is a rare selective disorder that consists of the disturbing and abnormal feeling of familiarity for unknown faces, while recognition of known faces is normal. In one such patient we investigated with a multimodal neuroimaging design the hitherto undescribed neural signature associated with hyperfamiliarity feelings. Behaviorally, signal detection methods revealed that the patient's discrimination sensitivity between familiar and unfamiliar faces was significantly lower than that of matched controls, and her response criterion for familiarity decisions was significantly more liberal.

Association between major mood disorders and the hypocretin receptor 1 gene.

Background: Recent studies suggested a role for hypocretins in the neurobiology of Major Mood Disorders (MMD). The purpose of this study was to investigate hypocretin involvement in MMD evaluating whether particular alleles or genotypes of the hypocretin pathway genes (HCRT, HCRTR1 and HCRTR2) would modify the occurrence and clinical features of the disease.

Methods: We selected for the study 229 MMD patients and 259 healthy age-, sex- and ethnicity-matched controls.

Cluster headache is associated with the alcohol dehydrogenase 4 (ADH4) gene.

Background/objectives: Alcohol is a well-known trigger factor for cluster headache attacks during the active phases of the disease. The alcohol dehydrogenase (ADH) pathway, which converts alcohol to the toxic substance acetaldehyde, is responsible for most of the alcohol breakdown in the liver. Humans have 7 ADH genes, tightly clustered on chromosome 4q21-q25, that encode different ADH isoforms.