Involvement of the Protein Ras Homolog Enriched in the Striatum, Rhes, in Dopaminergic Neurons’ Degeneration: Link to Parkinson’s Disease

Rhes is one of the most interesting genes regulated by thyroid hormones that, through inhibition striatal cAMP/PKA pathway, acts as a modulator dopamine neurotransmission. mRNA expressed at high levels in dorsal striatum, with medial-to-lateral expression gradient reflecting that both D2 and adenosine A2A receptors. transcript also present hippocampus, cerebral cortex, olfactory tubercle bulb, substantia nigra pars compacta (SNc) ventral tegmental area rodent brain. In line Rhes-dependent regulation dopaminergic transmission, data showed lack enhanced cocaine- amphetamine-induced motor stimulation mice. Previous studies pharmacological depletion significantly reduces rodents, non-human primates Parkinson’s disease (PD) patients, suggesting link between innervation physiological expression. protein binds to activates mTORC1, modulates L-DOPA-induced dyskinesia PD models. Finally, involved survival mouse midbrain neurons SNc, thus pointing towards modulation autophagy mitophagy processes, encouraging further investigations about mechanisms underlying dysfunctions nigrostriatal system.