Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits.

摘要: Abstract Neurotransmitters, such as γ-aminobutyric acid, glutamate, acetyl choline, glycine and the monoamines, facilitate crosstalk within central nervous system. The designated neurotransmitter transporters (NTTs) both release take up neurotransmitters to from synaptic cleft. NTT dysfunction can lead severe pathophysiological consequences, e.g. epilepsy, intellectual disability, or Parkinson's disease. Genetic point mutations in NTTs have recently been associated with onset of various neurological disorders. Some these trigger folding defects proteins. Correct is a prerequisite for export endoplasmic reticulum (ER) subsequent trafficking their pertinent site action, typically at plasma membrane. Recent studies uncovered some key features molecular machinery responsible transporter protein folding, e.g., role heat shock proteins fine-tuning ER quality control mechanisms cells. therapeutic significance understanding events apparent rising number reports, which directly link different pathological conditions misfolding. For instance, folding-deficient variants human dopamine GABA infantile parkinsonism/dystonia respectively. From view, are amenable functional rescue by small molecules, known chemical pharmacological chaperones.