Journal of Alzheimers Disease & Parkinsonism
Open Access

Abstract

Several types of D2R and D1R heteroreceptor complexes were discovered in the indirect and direct pathways of the striatum,
respectively. Changes in the function of the DA heteroreceptor complexes may help us understand the molecular mechanisms
underlying the motor complications of long-term therapy in Parkinson’s Disease (PD) with levodopa and DA receptor agonists. In
the indirect pathway, the potential role of the A2AR-D2R, A2AR-D2R-mGluR5 and D2R-NMDAR heteroreceptor complexes in
PD will be covered; and in the direct pathway, the D1R-D3R, A1R-D1R, D1R-NMDAR and putative A1R-D1R-D3R heteroreceptor
complexes in PD will be covered. D1R and D2R heteroreceptor complexes in the brain open up a new understanding of the
wearing-off of the anti-Parkinson actions of levodopa and DAR agonists and the production of levodopa induced dyskinesias.
Today, it seems as if the major advantage of DA receptor agonists is that they can postpone, in early PD, the use of levodopa
which gives a higher incidence of dyskinesias in PD patients vs. ropinirole and pramipexol. The motor complications can involve
a reorganization of the D1R and D2R heteroreceptor complexes and a dis-balance of the D1R and D2R homomers versus non-
DA receptor homomers in the direct and indirect pathways. Through understanding these mechanisms, new strategies for the
treatment of motor function deficits in PD can be offered with reduced motor complications. However, the motor deficits due to
degeneration of non-dopaminergic neurons will remain.The relevance of interactions of the receptor protomers in the signaling
cascades and the transcriptional regulation will also be discussed including downstream target proteins.

Biography

Kjell Fuxe is a Professor of Histology at Karolinska Institutet since 1979. He was the Member of Nobel Assembly from 1986-2005. He achieved his Honorary Doctorates
at the Universities of Barcelona, Ferrara, Malaga, at Universite Claude Bernard, Lyon, at Marquis Guiseppe Scicluna International University Foundation and at the Albert
Einstein International Academy Foundation. He has received a significant number of awards and published over 1500 papers in neuroscience. 1209 of them are found
in Pubmed. His major achievements involve pioneering work on central monoamine neurons, the existence of volume transmission, receptor-receptor interactions in
heteroreceptor complexes and in neuro-endocrinology and neuro-psychopharmacology.