IJMS, Vol. 21, Pages 590: TGF-?/Smad3 Signalling Modulates GABA Neurotransmission: Implications in Parkinson`s Disease (International Journal of Molecular Sciences)

γ-Aminobutiryc acid (GABA) is found extensively in different brain nuclei, including parts involved in Parkinson’s disease (PD), such as the basal ganglia and hippocampus. In PD and in different models of the disorder, an increase in GABA neurotransmission is observed and may promote bradykinesia or L-Dopa-induced side-effects. In addition, proteins involved in GABAA receptor (GABAAR) trafficking, such as GABARAP, Trak1 or PAELR, may participate in the aetiology of the disease. TGF-β/Smad3 signalling has been associated with several pathological features of PD, such as dopaminergic neurodegeneration; reduction of dopaminergic axons and dendrites; and α-synuclein aggregation. Moreover, TGF-β/Smad3 intracellular signalling was recently shown to modulate GABA neurotransmission in the context of parkinsonism and cognitive alterations. This review provides a description of GABA neurotransmission and TGF-β signalling; their implications in PD; and the regulation of GABA neurotransmission by TGF-β/Smad3. There appear to be new possibilities to develop therapeutic approaches for the treatment of PD using GABA modulators.