Purinergic Receptors in Basal Ganglia Diseases: Shared Molecular Mechanisms between Huntington's and Parkinson's Disease

Autor(es):Mostrar menos -

Glaser, Talita ; Andrejew, Roberta ; Oliveira-Giacomelli, Agatha ; Ribeiro, Deidiane Elisa ; Marques, Lucas Bonfim ; Ye, Qing ; Ren, Wen-Jing ; Semyanov, Alexey ; Illes, Peter ; Tang, Yong ; Ulrich, Henning

• Tipo de documento: Artigo Científico
• Fonte: NEUROSCIENCE BULLETIN; v. 36, n. 11, p. 16-pg., 2020-10-07.

Resumo

Huntington's (HD) and Parkinson's diseases (PD) are neurodegenerative disorders caused by the death of GABAergic and dopaminergic neurons in the basal ganglia leading to hyperkinetic and hypokinetic symptoms, respectively. We review here the participation of purinergic receptors through intracellular Ca(2+)signaling in these neurodegenerative diseases. The adenosine A(2A)receptor stimulates striatopallidal GABAergic neurons, resulting in inhibitory actions on GABAergic neurons of the globus pallidus. A(2A)and dopamine D2 receptors form functional heteromeric complexes inducing allosteric inhibition, and A(2A)receptor activation results in motor inhibition. Furthermore, the A(2A)receptor physically and functionally interacts with glutamate receptors, mainly with the mGlu5 receptor subtype. This interaction facilitates glutamate release, resulting in NMDA glutamate receptor activation and an increase of Ca(2+)influx. P2X7 receptor activation also promotes glutamate release and neuronal damage. Thus, modulation of purinergic receptor activity, such as A(2A)and P2X7 receptors, and subsequent aberrant Ca(2+)signaling, might present interesting therapeutic potential for HD and PD. (AU)

• Processo FAPESP: 18/17504-5 - Efeitos comportamentais e moleculares da modulação farmacológica dos receptores P2Y2 em modelo animal da Doença de Alzheimer
• Beneficiário: Deidiane Elisa Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/24553-5 - O papel do receptor P2Y1 na Doença de Parkinson
• Beneficiário: Roberta Andrejew Caetano
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/13345-1 - Doença de Huntington: envolvimento de Huntingtin no controle do comprometimento celular
• Beneficiário: Talita Glaser
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/26852-0 - Estudo do antagonismo de receptores purinérgicos no processo inflamatório e ativação microglial em modelos in vivo e in vitro de Doença de Parkinson
• Beneficiário: Ágatha Oliveira Giacomelli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/07366-4 - Receptores de purinas e cininas como alvos de estudo e intervenção terapêutica em doenças neurológicas
• Beneficiário: Alexander Henning Ulrich
• Modalidade de apoio: Auxílio à Pesquisa - Temático