Pulmonary Drug Discovery & Therapy (Track)


Julianna Kardos

Director, Institute of Molecular Pharmacology Research Centre for Natural Sciences, Hungarian Academy of Sciences Pusztaszeri ut 59-67., 1025 Budapest, Hungary.


Epilepsy, the most common chronic neurological disorder, affecting almost 1% of the population worldwide is characterized by periods of abnormal, hypersynchronous neuronal activity. Therefore, epilepsy research has traditionally focused on neurons, while neglecting the contribution from non-neuronal cells. However, several lines of evidence have unequivocally shown that many of idiopathic epilepsies have non-neuronal origins. It is important in this context that astrocytes possess the complete set of membrane proteins to detect gamma-aminobutyric acid and glutamate. Thus, both GABAergic and glutamatergic neurotransmission are modulated by neuro-glia coupling, and pathophysiological alterations of astrocytic function have been shown to influence neuronal excitability and transmission. It is also demonstrated in vivo and during enhanced network activity in vitro that the uptake of Glu by glial cells is coupled to the subsequent reversal of the glial GABA transporter bringing about an elevation of ambient GABA, thereby increasing the tonic inhibition of neurons. Rescuing neurons from harmful over-excitation, the negative feedback mechanism outlined can form the basis of an innovative therapeutic strategy that is able to overcome the limitations of current anti-epileptic drugs.