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

Involvement of the protein ras homolog enriched in the striatum, rhes, in dopaminergic neurons’ degeneration: Link to parkinson’s disease

Serra M.;Costa G.;Morelli M.;
2021

Abstract

Rhes is one of the most interesting genes regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine neurotransmission. Rhes mRNA is expressed at high levels in the dorsal striatum, with a medial‐to‐lateral expression gradient reflecting that of both dopamine D2 and adenosine A2A receptors. Rhes transcript is also present in the hippocampus, cerebral cortex, olfactory tubercle and bulb, substantia nigra pars compacta (SNc) and ventral tegmental area of the rodent brain. In line with Rhes‐dependent regulation of dopaminergic transmission, data showed that lack of Rhes enhanced cocaine‐ and am-phetamine‐induced motor stimulation in mice. Previous studies showed that pharmacological de-pletion of dopamine significantly reduces Rhes mRNA levels in rodents, non‐human primates and Parkinson’s disease (PD) patients, suggesting a link between dopaminergic innervation and physiological Rhes mRNA expression. Rhes protein binds to and activates striatal mTORC1, and modulates L‐DOPA‐induced dyskinesia in PD rodent models. Finally, Rhes is involved in the survival of mouse midbrain dopaminergic neurons of SNc, thus pointing towards a Rhes‐dependent modulation of autophagy and mitophagy processes, and encouraging further investigations about mechanisms underlying dysfunctions of the nigrostriatal system.
3,4‐methylenedioxymethamphetamine (MDMA)
Autophagy
Huntington’s disease
L‐Dopa‐induced dyskinesia (LID)
Mitophagy
MTOR
Substantia nigra
SUMO E3 ligase
Animals
Autophagy
Brain
Corpus Striatum
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Dopaminergic Neurons
GTP-Binding Proteins
Gene Expression Regulation
Humans
Levodopa
Mice
Mice, Knockout
Mitophagy
Models, Neurological
Nerve Degeneration
Parkinson Disease
Parkinsonian Disorders
RNA, Messenger
Signal Transduction
Synaptic Transmission
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11584/325361
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
social impact