Repurposing GLP-1 Receptor Agonists for Parkinson's Disease: Current Evidence and Future Opportunities

Autor(es)

Victorino, Daniella Balduino ^[1] ; Nejm, Mariana ^[1] ; Guimaraes-Marques, Marcia ^[1] ; Scorza, Fulvio Alexandre ^[1] ; Scorza, Carla Alessandra ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Paulista Med Sch, Dept Neurol & Neurosurg, Discipline Neurosci, Pedro Toledo 669, 1st Floor, BR-04039032 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICAL MEDICINE; v. 35, n. 1 JAN 2021.
• Citações Web of Science: 0

Resumo

The global burden of chronic disorders such as Parkinson's disease (PD) has rapidly increased over recent decades. Despite an increasing understanding of PD pathophysiology, there are no effective therapies capable of stopping or slowing the progression of this neurological condition. It has been suggested that type 2 diabetes mellitus (T2DM) may be a risk factor for PD and comorbid T2DM may worsen PD symptoms, as well as accelerate neurodegeneration. In fact, the similar pathological mechanisms shared by PD and T2DM have inspired several studies on the therapeutic potential of T2DM drugs against PD, among which glucagon-like peptide-1 receptor (GLP-1R) agonists are promising candidates. Here, we highlight the mechanisms linking T2DM and PD, as well as the links between insulin resistance (IR) and PD patients' risk of developing cognitive deficits. We also briefly review the effects of GLP-1R agonists on PD and discuss how the successful use of these substances in preclinical models of PD has paved the way for PD clinical trials. We further discuss how recent evidence on the beneficial effects of dulaglutide on cognitive function of T2DM patients may have important implications for PD drug repurposing. (AU)

• Processo FAPESP: 16/17746-3 - Avaliação dos efeitos de benzodiazepínicos sobre a atividade eletrofisiológica cerebral in vivo e a viabilidade neuronal in vitro em camundongos da linhagem Ts65Dn
• Beneficiário: Daniella Balduino Victorino
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/18568-7 - A Privação de sono e suas possíveis alterações cardíacas em um modelo da Doença de Parkinson induzida por 6-hidroxidopamina em ratos: compreensao para a morte súbita na Doença de Parkinson (SUDPAR).
• Beneficiário: Fulvio Alexandre Scorza
• Modalidade de apoio: Auxílio à Pesquisa - Regular