GBA-associated Parkinson's disease in Hungary: clinical features and genetic insights.

Introduction: Parkinson's disease (PD) has a complex genetic background involving both rare and common genetic variants. Although a small percentage of cases show a clear Mendelian inheritance pattern, it is much more relevant to identify patients who present with a complex genetic profile of risk variants with different severity. The ß-glucocerebrosidase coding gene (GBA1) is recognized as the most frequent genetic risk factor for PD and Lewy body dementia, irrespective of reduction of the enzyme activity due to genetic variants.

Loop F of the GABA receptor alpha subunit governs GABA potency.

Gamma-amino butyric acid (GABA) is an abundant neurotransmitter in the CNS. GABAergic interneurons orchestrate pyramidal neurons in the cerebral cortex, and thus control learning and memory. Ionotropic receptors for GABA (GABAR) are heteropentameric complexes of α, β and γ integral membrane-protein subunits forming Cl -channels operated by GABA, which are vital for brain function and are important drug targets.

Sarcosine-Based Glycine Transporter Type-1 (GlyT-1) Inhibitors Containing Pyridazine Moiety: A Further Search for Drugs with Potential to Influence Schizophrenia Negative Symptoms.

We have synthesized a novel series of N-substituted sarcosines, analogues of NFPS (N-[3-(biphenyl-4- yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine), as type-1 glycine transporter (GlyT-1) inhibitors. Several compounds incorporated a diazine ring inhibited recombinant hGlyT-1b expressed permanently in CHO cells and GlyT-1 in rat brain synaptosomal preparations. A structure-activity relationship for the newly synthesized compounds was obtained and discussed on the ground of their GlyT-1 inhibitory potencies.

Temporal alteration of spreading depression by the glycine transporter type-1 inhibitors NFPS and Org-24461 in chicken retina.

We used isolated chicken retina to induce spreading depression by the glutamate receptor agonist N-methyl-d-aspartate. The N-methyl-d-aspartate-induced latency time of spreading depression was extended by the glycine(B) binding site competitive antagonist 7-chlorokynurenic acid. Addition of the glycine transporter type-1 inhibitors NFPS and Org-24461 reversed the inhibitory effect of 7-chlorokynurenic acid on N-methyl-d-aspartate-evoked spreading depression.

(Phenylpiperazinyl-butyl)oxindoles as selective 5-HT7 receptor antagonists.

A series of potent 5-hydroxytryptamine 7 (5-HT 7) ligands has been synthesized that contain a 1,3-dihydro-2 H-indol-2-one (oxindole) skeleton. The binding of these compounds to the 5-HT 7 and 5-HT 1A receptors was measured. Despite the structural similarity of these two serotonin receptor subtypes, several derivatives exhibited a high selectivity to the 5-HT 7 receptor.