Annals of neurosciences
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Annals of neurosciences · Apr 2011
ReviewEmerging role of WNK1 in pathologic central nervous system signaling.
WNK1 (with no lysine (K)) is a widely expressed serine/threonine protein kinase. The role of this kinase was first described in the kidney where it dynamically controls ion channels that regulate changes in cell volume. WNK1, through intermediates oxidative stress-responsive kinase-1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK), phosphorylates the inwardly directed Na(+)-K+-Cl(-)--cotransporter 1 (NKCC1) and the outwardly directed K(+)-Cl(-)-cotransporter 2 (KCC2), activating and deactivating these channels, respectively. ⋯ Growing evidence implicates WNK1 playing a critical role in pathologic nervous system signaling where changes in intracellular ion concentration in response to γ-aminobutyric-acid (GABA) can activate otherwise silent pathways. This review will focus on current research about WNK1, its downstream effectors and role in GABA signaling. Future perspectives include investigating WNK1 expression in the CNS after spinal cord injury (SCI), where altered neuronal signaling could underlie pathological states such as neuropathic pain (NP).
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Annals of neurosciences · Apr 2010
ReviewThe current status of gene therapy for Parkinson's disease.
The recent development of viral vectors, especially vectors derived from adeno-associated virus (AAV), has translated gene therapy for Parkinson's disease (PD) from animal experiments into clinical trials. The current gene therapy protocols used are based on three major strategies. The first protocol involves local production of dopamine via the introduction of dopamine-synthesizing enzyme genes into the putamen. ⋯ The second protocol involves the protection of nigrostriatal projections via the production of neurturin, a trophic factor for dopaminergic neurons in the putamen. The final method includes the modulation of neural activity along the output pathway of the basal ganglia by transducing the subthalamic nucleus with vectors expressing glutamic acid decarboxylase (GAD-65, GAD-67), a key enzyme required for the synthesis of the inhibitory transmitter -aminobutyric acid (GABA). The initial results of phase 1 studies using AAV vectors have not only confirmed the safety of these vectors, but have also revealed the alleviation of motor symptoms associated with PD.